Dextromethorphan used for PD Protection

[ashleyk]

There have been posts here on the search for drugs that could be neuroprotective for people with Parkinson's. It's possible that there may be some drugs available now that can be used off-label to slow or stop the progression of PD. The drugs that I've come across are in the opioid receptor antagonist class and one of them is cough syrrup, Dextromethorphan, sold over the counter. Another is Naltrexone or low dose naltrexone which I have been taking for 28 months. My PD does not seem to be worse over that time but maybe that's because of the sinemet and not enough time has passed.
On the old forum, before it crashed and burned, there was a member, RLSmi, who said he was taking Simply Cough which has Dextromethorphan as it's active ingredient. I noticed that RLS has joined this forum. I saved his old post on the other site and re-posted below. Hope you don't mind RLS. I found it interesing and hopeful, if I lose my LDN source, I will probably be taking DM. If you see this post RLS, would like to know how you are doing and if you still see DM as a drug to stop or slow PD progression.
I have also posted research by Dr. Hong of the NIH on DM below. I also emailed him about LDN and he said it's worth taking but he's not sure about dosage.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=15790998&dopt=Abstract

Regards, Ashley

RLSmi
Braintalk 04/12/06
Join Date: Sep 2004
Posts: 93
Default *Attempting neuroprotection with DM*
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The third link Ashleyk listed in her post describes research on neuroprotection in a mouse model of PD using the drug Dextromethorphan (DM). DM is in the same class of drugs as naltrexone, which also has neuroprotective effects in the same system. Because DM is availablae over the counter, I have been taking it instead of naltrexone daily for more than a year at a dose of 5 mg, along with sinemet, amantadine and high-dose CoQ10. I am four years into my PD Dx, and I may still be in the sinimet honeymoon period, but my wife and I both think that something is keeping my symptoms from progressing.

At WPC I spoke with Dr. Jau-Shyong Hong, the senior author of the article mentioned above, after a presentation he made there on the role of glial cell inflammation in PD. His research group in North Carolina has been working on the mechanism of action of these drugs and the natural hormone dynorphin in neuroprotection. He was very interested in my story and we have been in communication about this several times since then. He hinted that there may be trials using DM for PD neuroprotection either planned or going on in other countries.

DM is most commonly used in cough medicines that also contain other active ingredients, and Dr. Hong was emphatic in specifying that any attempts at using it for neuroprotection should be with a preparation in which DM alone was the active ingredient. The preparation I am currently using is called Simply Cough. It is manufactured by McNeil Laboratories, who also make Children's Tylenol. When I described this process on this thread several months ago, someone added the precaution that DM should not be taken by someone also taking a MAO inhibitor.

Although I do not recommend that others start using DM, it seemed appropriate to post this information on this neuroprotection thread.
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/ Last edited by RLSmi : 04-13-2006 at 01:28 AM.

[RLSmi]

I have just now read your posting from yesterday.

Yes, I am still taking dextromethorphan in the form of the cough syrup "Simply Cough" each night before I turn in. The rest of my medication remains as it was when I described it earlier.

I am pleased to report that my symptoms do not seem to have progressed since starting this regimen. I am only 5 years into my diagnosis, though, and sinemet "honeymoons" have been known to last 10-15 years.

Perhaps the best indication of non-progression, or at least slowed progression, is the fact that my daily carbidopa/levodopa is only 2X50/200mg CR, plus one-half of a regular 25/100mg tablet for a morning "jump start."
CoQ10 is 900mg, amantadine 100mg, plus extra vitamin E and C, two multivitamins, Effexor and Welbutrin daily.

I have not heard directly from Dr. Hong lately, but have been keeping up with his scientific publications.

Last month, a former vice-president for research for Merck visited in our department. Since this man's special interest is neuroscience, I told him about my Dx and my use of DM. I described Hong's work to him, and showed a lot of interest in it and asked me for a copy of his latest publication in which he described similar supression of mouse midbrain inflammation by other recently discovered natural protein neurohormones and small fragments (peptides) derived from them.
I expect to eventually hear about clinical trials with DM in PD that may have already begun in Taiwan.

Robert

[ashleyk]

Hi Robert, good to hear from you and that you're doing ok with the DM. One question I had was how do you measure out your 5 mg dose of Simply Cough?
I also don't know how to determine if 28 mo's of 4.5 mg naltrexone daily, LDN, is keeping me from progressing except to continue with it and hope. I assume, I too am in the sinemet honeymoon. When I first started sinemet 24 mo's ago, the neuro had me at 3x 25/100 a day. Over a year ago, I have cut back to about 1x sinemet a day but I was also given 2x 0.25 Mirapex. Tremor was my main problem and that's gone. I would like to say I have not progressed because of LDN. I also take 200 mg of Q10, magnesium and am about to start Tumeric, all supplements that I've learned about on Braintalk.

Dr. Hong and his people at the NIH seem to have come across a class of drugs such as DM and naloxone that, used at very low doses, seem to slow or stop disease causing neuroinflamation. Their work is done with mice and they are able to quickly determine the effects of these drugs. The problem with PD is that the disease is variable so how would they do clinical trials on people? Even if these drugs are shown to really work, it will be years before they are released. The big drug companies would have to spend millions in research and trials on simple drugs that exist now with their patents expired. There's no money in it for them. That's why I am not waiting, DM and LDN are known and relativly safe with few side effects. Since DM cough syrrup is available over the counter, I thought if people are interested, I would post Dr. Hong's research on opioid recetptor atagonists and they could go from there.
Ashley

[/URL]
[URL]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=12649371&dopt=Abstract (http://jpet.aspetjournals.org/cgi/content/full/319/2/595)

Mechanistic studies indicated that the neuroprotective effect of DM is mediated through the inhibition of microglia over-activation (18) . In the course of attempting to determine DM’s action site, we realized that the inhibitory effect of DM on the production of superoxide mimicked the effect of dynorphins at femtomolar concentrations (19) . This comparison led us to study the neuroprotective effect of DM at femtomolar concentrations. In this paper, we report the extremely unusual and exciting finding that femtomolar concentrations of DM exert an effect as efficient as micromolar concentrations of DM in protecting dopaminergic neurons against LPS-induced damage. We have elucidated the underlying mechanism for this femtomolar acting compound’s neuroprotective effect. DM has been used clinically for decades with a proven safety record and it is a small molecule that can be administered orally, suggesting that DM is an ideal remedy for long-term usage for neurodegenerative diseases. In view of the lack of therapeutic agents that can halt the progression of PD, our findings may provide a novel therapy for these neurodegenerative diseases.

[RLSmi]

and the other substances Hong's group have been testing at such low concentrations is a total mystery to me. I am not aware of any precedent for the known opioid receptors one would expect to be involved to be responsive to any drug or natural ligand in the femtomolar concentration range. This is thousands of times lower than observed with other opioid effects.

They have clearly demonstrated that the critical enzyme that is inhibited is the NADPH oxidase of microglial cells. This is a complex intracellular enzyme which uses a one-electron transfer to molecular oxygen to generate the superoxide ions released when lipopolysaccharide (LPS) activates the process through a cell-surface LPS receptor. This system is part of the intrinsic immune system in the brain which serves to kill invading microorganisms that have LPS in the structure of their cell wall.

Somehow, these femtomolar-effective molecules are interfering with this process. Invoking an ordinary ligand-receptor equilibrium to achieve this at such low concentrations makes a physical chemist squirm and a medicinal chemist start thinking "homeopathy." The apparent dissociation energy in such a reaction is more typical of a stable covalent bond.

I would be interested to see if the activity of the enzyme in these microglial cell cultures returns after medium containing the drug was replaced with drug-free medium. I may give the good doctor a call on that next week!

Sorry to bore you folks with this, but writing it out it has helped me to see this phenomenon from a different angle.

Robert

[ol'cs]

Well ya got a central nervous system senior research scientist (chemist) in the crowd somewhere around here, I don't know who he is, but he's a bit forgetfull these days.:o :D (he's a bit daft and has a difficult time doing things like erasing his own posts, because his fingers keep hitting the wrong buttons when he's all dyskinetic:D ).
I don't think one has to get quite into the explanations for DEX as has been stated. DEX is the mirror image of LEVOMORPHAN, which is a narcotic mu agonist.

"Dextromethorphan crosses the blood-brain barrier, and the following pharmacological actions have been reported:

NMDA glutamatergic receptor antagonist
Dopamine reuptake inhibitor[3]
σ1 and σ2 receptor agonist (Zhou & Musacchio, 1991)
α3β4 nicotinic receptor antagonist[4]
Serotonin reuptake inhibitor[5]"

Now this gets back to a discussion that we had awhile back where, I believe it was fiona who asked something about low dose Naltrexone (which is a dopamine antagonist). During this discussion, this medicinal chemist (wish I could remember his name!:o ) started a line about his believing that narcotic agonists, and antagonists bear a superficial resemblance to Apomorphine, where, if you look at that molecules structure has the dopamine structure "buried" in what we would call a lipophilic molecule, and lipophilic molecules are often brain penetrable, so they have "CNS effects". Nearly all narcotics of the "phenanthrene" class have the dopamine structure embedded within them, and have "extra structural details" that allow the molecule increased lipophilicity ("fat loving", increased solubility in fatty tissue) which is a property involved in passive blood brain barrier penetration of a molecule, since the brain is literally all fat no muscle.
So, these types of molecules get into the brain, wheras dopamine itself can't. The fact that the dopamine structure is preserved in the larger molecule, is unquestionable to say that these molecules could have dopaminergic effects. I noticed it from Oxycontin. Therapeutic doses allowed me to cut my sinemet intake by half. And now, using Apomorphine, a molecule devoid of narcotic properties, but still retaining the dopamine structure within the molecule, and the most potent dopamine agonist known; the user suggests that in the phenanthrene like molecular structure, there lies the next best chance at creating the next "best D agonist", one with no emetic effects, a long half life, orally active, easy on the liver enzymes, and most of all, being a blockbuster antiparkinson drug.
HOwever, we're not there yet and we don't even know if anybody is working on it; most of the pharma companies bowing to the supremecy of Dopa. Many pharm companies that had active D agonist projects just stopped pouring money into this area. IN fact, CNS D agonism is considered a liability as far as receptor binding profiles of new "ethical" drug discovery.
In a nutty shell, Dextromethorphan may be a simple weak D agonist, a molecule whose properties as far as they relate to an antiparkinsons drug which have not been optimized.
That's how an old school pharmaceutical discovery science would at first look at the reported phenomenon that is reported for this molecule. Femtomolar uncharacterized enzyme inhibitory effects is a good reason not to pour money into it's further investigation, but relate it to apomorphine's receptor binding profile, and dopamine structure similarities itself and you might get a few "experts" to give it some more thought. THat would be nice, but will it, or is it happening? Your guesses are as good as this guy I seem to know, what's his name, damn, I forget!:D
By the way, will somebody just open the door and let us out of here!:confused:

[ashleyk]

Hi, I've updated this old post on dextromethorphan (cough syrrup). I sort of changed the the subject on the BBB post which I didn't mean to do.
In the BBB thread, Steve disscuses his interesting improvements after being on dextromethorphan, DM, for only a few weeks. At first I thought his observations were a placebo effect of the DM. I then recalled a report on DM that I had read and went back to look at it and this report noted that DM can cause dopamine release. It's interesting and should be read by anyone thinking of using DM long term. It was written, I believe, on the concern that DM can be used at high doses to get high. Anyway, there are some interesting points in this long report (para 3.2, 3.3, 3.4). I suspect Steves improvements may be due to the DM creating more dopamine and maybe the DM is also being neuroprotective. This is territory where we should be careful. Try to get all the info you can if you intend to go DM longterm. DM cough syrrup has been around a few decades?, it's currious that Steves improvements have not been noted by the medical profession (or have they?).
If you read the research done by Dr. Hong, Head of Pharmacology at the NIH, he has observed that DM used at very low doses in rodents can be neuroprotective.
Ashley

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=15790998&dopt=Abstract

<3.2> What are the side effects and risks of chronic DXM use?

Prolonged, regular use of DXM has some definite risks. The
most common is mania; this has been reported in people who used large
amounts of DXM (especially to self-medicate depression) (1-3). Some
research has linked sigma receptors to schizophrenia (46-49), and
chronic use of NMDA antagonists has been shown to upregulate
(increase) dopamine receptors (50). This could theoretically mean
that DXM could trigger schizophrenia in susceptible individuals,
although nobody knows for sure. DXM could also decrease immune
function due to sigma activity (51). One thing that is known is that
neither DXM nor PCP nor ketamine cause any change in PCP or sigma
receptors.
Another possible effect of long-term DXM use is neurotoxicity.
This has not been observed, but would be consistent with DXM's
hypothesized ability to induce 5HT and dopamine release (52). Such
neurotoxicity would probably be restricted to 5HT (serotonin) neurons,
and be similar to the neurotoxicity resulting from use of MDMA
(ecstasy). Note that no animal studies have ever demonstrated this.
Chronic use of NMDA antagonists seems to modify alcohol
tolerance; this is based mostly on anecdotal evidence and theory, but
it appears to be a very real phenomenon. If true, then it is
important to note that the GABA receptor effects of alcohol may NOT be
changed; in practical terms, you might be a lot drunker than you feel,
and this could possibly lead to alcohol poisoning. Be careful, and
limit yourself to as little alcohol as possible when using DXM. A
recent paper supports the ability of DXM to affect alcohol tolerance
(53).


Reason to believe DM could work at very low doses:
Dr Hong, Head of Pharmacology, NIH

Findings from our research not only reveal an extremely unusual and interesting femtomolar acting compound, but also raise a new concept of using "ultra-low" concentrations of drugs for future therapeutic interventions for inflammation-related diseases. Although whether these in vitro findings can be substantiated in animal studies and eventually tested in clinical trials remain to be studied, the obvious advantages of this low-dose therapy, including the much reduced side effects warrants serious consideration of this approach. To obtain a preliminary glimpse, we have recently observed in an animal study that 100 million-fold lower than the regular dose of DM was effective in reducing the plasma level of alanine aminotransferas (ALT) in LPS/D-galactosamine-induced liver damage (unpublished observations). It is very surprising to learn that DM in such low concentrations is still effective to possess anti-inflammatory effect. However, in view of its potent inhibitory effect on the flavo-containing enzyme (PHOX) we have studied, which is one of the contributors of proinflammatory factors, may explain its potent anti-inflammatory potency and justify further studies of DM or its analogs using different animal models of inflammation.

[reverett123]

Very promising, actually. Been around fifty ears. Lot of recreational freelancers taking up o fifty times the normal dose without noticing bad effects. Lasts up to eight to twelve hours. Makes your dopamine go farther so hopefully yo can cut back on the darned stuff.

I, for one, am going to give it a trial once I give my mao inhibitor a couple of weeks to clear out.

As to the lack of research, may I suggest that when the patent expired that there was no reason to put money into competeing with the new wonder drug levodopa.

I will dutifully report on my experience.

#%%^!@@ ...Ground Control to Major Tom...)))*^&&%
$$)*%@@# Houston, we have a problem. Tom forgot the munchies...:D




From wikipedia (so take with one grain of salt):

At therapeutic doses, the drug acts centrally to elevate the threshold for coughing, without inhibiting ciliary activity. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, and metabolizes within 15 to 60 minutes of ingestion. The duration of action after oral administration is approximately three to eight hours for dextromethorphan-hydrobromide, and ten to twelve hours for dextromethorphan-polistrirex. Because administration of DXM can trigger a histamine release (an allergic reaction), its use in atopic children is very limited.

The average dosage necessary for effective antitussive therapy is between 10 mg and 30 mg. The time to re-dose depends on the specific preparation being used.


Side-effects of dextromethorphan use can include body rash/itching, nausea as well as other gastrointestinal disturbances, drowsiness, dizziness, excitation, vomiting, blurred vision, dilated pupils, sweating, fever, hypertension, shallow respiration, urinary retention, and increases in heart rate, blood pressure, and body temperature.[5]

Dextromethorphan can also produce psychological dependence due to its potential for recreational use, but does not produce physical addiction, according to the WHO committee on Drug Dependence.

Dextromethorphan, when combined with guaifenesin, an expectorant used in many preparations, is likely to cause nausea and vomiting when the combination is taken at recreational doses.

Dextromethorphan should not be taken with any of the following:

* monoamine oxidase inhibitors (MAOIs)[5]
* selective serotonin reuptake inhibitors (SSRIs)[5]
* CNS depressant drugs and substances, including alcohol, antihistamines, and psychotropics, will have a cumulative CNS depressant effect if taken with dextromethorphan.[5]


Dextromethorphan was first patented with U.S. Patent 2,676,177 .<1954>

The FDA approved dextromethorphan for over-the-counter sale as a cough suppressant in 1958. This filled the need for a cough suppressant lacking the sedative side-effects, stronger potential for abuse, and physically addictive properties of codeine phosphate, the most widely-used cough medication at the time (now prescription-only in the United States).[11] As with most cough suppressants, studies show that dextromethorphan's effectiveness is highly debatable.[2] See also: Cough medicine controversy

During the 1960s and 1970s, DXM became available in an over-the-counter tablet form by the brand name Romilar. It was put on the shelves in hopes of cutting down on codeine cough remedies. In 1973, Romilar was taken off the shelves after a burst in sales due to common recreational use. It was then replaced by cough syrup, in an attempt to cut down on recreational usage.[11]

More recently (around 2000) gel capsule forms began reappearing in the form of Robitussin CoughGels as well as several generic forms of that preparation.

[ol'cs]

It still has not been scientifically proven that ANY compound known exhibits "neuroprotective" properties IN VIVO. There are compounds on the market that are in use with the blessing of the FDA for use in alzheimers disease, but their effects are mainly attributed to their anticholinergic activity. We worked for years barking up the "neuroprotective" tree and found that all we ever came up with just showed certain human cell lines aged a bit slower in media treated with some of the compounds we had made. Nothing that the FDA would buy, so we dropped all research in this area.
But I would never discourage any researcher from keeping on trying, and maybe, just maybe something will come up in the future. And just as a footnote, "neuroprotective" agents are all the rage in Japan, where rules for allowing drugs on the market are more lax. In other words you can claim neuroprotection without ever proving it, as long as your compound is pretty well "dead" as far as having any other possibly detrimental physiological effects.

[stevem53]

I cant hardly tell what you folks are talking about..:confused: :D ..All I can say is that Ive consistantly felt alot better symptomatically than I have in approx 2 years..with the exception of today because I have a wicked stomach bug going on..uggghh!..got a case of the watery runs etc..not fun..:( ..feverish..So when I feel better I will make a list of the changes in symptoms

[stevem53]

I happened to research Rasagiline, and with my very limited education on chemistry I got the notion that it does something similar to DM in the dopamine reuptake inhibitor dept..Am I on the right track here or am I out in left field with that assuption?

[reverett123]

<Heresy Alert!>....is not the only way to gather knowledge nor is it always the best way. And it is particularly in question in the case of a patient with a progressive disease. (I'm not sure how I got started on this but I think it was ol cs reminding me of the whole "no neuroprotection" fiasco.)

So maybe this is a bit off topic, but actually the dex situation is a good one to bring it up. Suppose standard procedure rules and dex has to pass through the whole FDA process. First, no one has much financial incentive to fund research, so even if it was a blippin cure it might never see the light of day. And if some foundation eventually decided to fund it, they would start with a rat. Then they'd need more funding for a primate study. Then more for a Phase 1, etc, etc.

So here is an ancient drug that we've been giving to babies for forty years with good reason to suspect great things about it for PWP. Dosage safety has been stress-tested on the streets at ridiculously high levels with positive results. It's dirt cheap. And still figure on twenty years minimum before you can legally use it for PD.

There's an idea being floated around by one of the advocacy groups that I really like. Compile a database of things with a reasonable expectation of benefit and safety. Then work with patient volunteers who, with the supervision of their own doctors, gingerly test them. Compile the data and let each of us make our own decisions.

Now, that's science. OK, a bit down and dirty, but effective.:)
End of rant and back to topic. My apologies.

[stevem53]

The two very distict things that I noticed was that I slept sounder and was energetic in the morning..I am still enegetic in the morning, but the quality of my sleep has reverted back to "normal"..actually I am energetic throughout most of the day, except I still have to take a mid-day nap..Ive noticed that even when I start to experience the mid-day fatigue, I still seem to maintain most of the newfound movement ability..I feel motivated, as I was having alot of trouble getting motivated to leave the house..to get dressed, to get undressed all semed like a hassle..It was getting easy to talk myself into staying home, but then..to do what?..My condition was making me uncomfortable..I go to a few AA meetings a week, and it is something that I always look foward to doing..but when I think about navigating through the crowd, just sitting there any feeling physically uncomfortable..the hassle it is just to go over to the coffee pot and get a cup of coffee, without spilling it on the way back to my seat..the feeling of holding everybody else up because Im so slow..cant seem to walk by people without bumping into them..its cold out..I think about that stuff and its enough to make me want to stay home, and thats exactly what Ive done sometimes..It felt like my whole body was parkied up all the time..I dont have that mental battle going on now because I feel more confident in my movements..Im not uncomfortable anymore

Pd was beginning to effect my left side as well..I noticed that I began knocking objects over with my left hand as well..I began to have difficulty picking up mail, a piece of paper etc from the table with my left hand..my balance was beginning to deteriorate..I began having near falls, where I had just enough balance ability to right myself before taking a fall..I began having difficulty putting my belt through the loops with both hands, whereas it was only with my right hand before..putting my pants on, my right foot usually get stuck in the pant leg because the ankle wont bend to slip it in..Putting my hands behind my back to take my coat off was a challenge..streeeeeeeeeccch!..getting in my truck was getting more difficult because I have to put my bad side in first..lifting my right leg high enough to clear the rocker panel was difficult, and would usually end up having my butt half on the seat when I got in, and then shimmy across the seat..Putting the key in the ignition was a chore..sometimes I had to literally put the key in the right position with my left hand, because if it was cocked I couldnt straighten it out with my right hand..then when I got the key in the ignition it was a strain to turn it all the way to engage the starter..my hand only wanted to turn the key 3/4 of the way..Putting the truck from park to drive, another hassle..and vice versa..drive to park was even worse..my gait was getting worse

None of these tasks are a problem anymore..the left side of my body is hardly symptomatic at all now..Im more confident walking, driving, doing daily chores..I feel motivated..energetic..my whole emotional balance has taken a turn for the better..What Ive noticed that is remarkable is that I can put my truck key in the ignition in the dark first shot 8 out of 10 times..I had trouble doing it in the daylight first shot if I was looking right at it..my typing ability has improved..Ive tried the toe tapping and doorknob turning drills that my neuro tests during his examination, and I can do them with more coordination..the doorknob turning was the hardest..no trouble with my left hand but my right hand would just sit there and tremble with hardly any movement whatsoever..now I can do it with my right hand but not with as much speed as my left..As I sit here today, I still havent completely gotten over this stomach bug, but still have alot of movement nonetheless

[reverett123]

And anyone else trying either drug, a question-

Have you noticed any change in the way stress affects you?

Thanks. -Rick

[stevem53]

So far I havent experienced any stressful situations other than that nasty stomach bug I had yesterday and part of today..I dont think anything would have helped that..I can tell you though that I feel a general feeling of relief..I am the secretary of a large AA group and I have to stand at a podium for about the first 10 minutes of the meeting, and I read from a script because I fear that I will start stuttering and wont be able to stop..I was more comfortable doing it last Wednesday..Thats about it for right now

[Thelma]

Everstt

Are you thinkilng the setative effect contains the stress they seem to indicate is relaxed a bit.

Thanks Thelma

[caya]

Steve:

Excuse my ignorance but I have been out-of-pocket for a while. What is it that you are doing to have such a great improvement in symptoms???? Are you taking the DM that the folks have been discussing? If so, how much are you taking each day. Congratulations on your good feeling these days.

Caya

[reverett123]

Everstt

Are you thinkilng the setative effect contains the stress they seem to indicate is relaxed a bit.

Thanks Thelma

Thelma-

Stress is a major player (perhaps THE major player) in PD deriving from our imbalanced neuroendocrine system and our screwed up cortisol levels. They are typically high for PWP. More importantly, where a normal production cycle peaks in the morning to help us wake up and drops as much as 90% over the course of the day, PWP have a steady rate of production without the morning peak. Bottom line is we have chronically elevated levels.

And that isn't good. One of the obvious things is that hypercortisolism sets us up for systemic inflammation which, among other things, opens the BBB and lets in toxins such as the bacterial LPS i have mentioned earlier. The reaction of the microglia then leads to the destruction of the substantia nigra and so on.

We have never received a good answer from our docs as to just why we are so sensitive to stress. Shake at the drop of a hat. Why? The answer lies here and it may be a clue as to part of the action of the dextromethorphan. As RLSmi pointed out, femtomolar concentrations are pretty darned tiny. Not what one would expect as effective sedation for something as "weak" as DM. Something more is at work and this may be close to it.

Notice that Steve felt calm, not groggy or sedated or similar feelings. And he woke up feeling good, not hung over or anything.

Getting more interesting by the day. -Rick

[stevem53]

Steve:

Excuse my ignorance but I have been out-of-pocket for a while. What is it that you are doing to have such a great improvement in symptoms???? Are you taking the DM that the folks have been discussing? If so, how much are you taking each day. Congratulations on your good feeling these days.

Caya

A half teaspoon of CVS brand maximum strength tussin cough syrup (15 mg per teaspoon) dextromethorphan every night before bed

[stevem53]

What Ive been wondering is this..DM is a dopamine reuptake inhibitor..I wonder if it causes the Sinamet to work more efficiently

[reverett123]

What Ive been wondering is this..DM is a dopamine reuptake inhibitor..I wonder if it causes the Sinamet to work more efficemtly

But what really got my interest was the "warning" about resensitizing of the receptor system. One way to skin the PD cat is to flood the system with dopamine figuring some will get through. That's more or less the sinemet approach.

The other is to optimize the receptor sensitivity and make a little dopamine go farther, which may be what is happening in part.

-Rick

[RLSmi]

has a brief explanation of LDN action based on previous work by Dr. Zagon and may also be what happens with low-dose DM. It goes something like this:
The small dose of of this opioid antagonist blocks certain opioid receptors for a short period of time just before the period of sleep in which the endorphins such as methionine enkephalin are produced by the adrenal and pituitary glands. This short inhibition stimulates increased production of endorphins and their opioid receptors in the brain.

If you want to read the actual text, here is the link to the site.
http://www.lowdosenaltrexone.org/index.htm
Since the endorphins and enkephalins are our natural "feel good" hormones, and are involved in regulating a varitey of cells of the immune system such as brain microglia, this combination of effects may be at the bottom of both Steve's lift in mood and the neuroprotection we are hoping for.
Robert

[vlhperry]

Stupid question: Would a combination of a teaspoon of cough syrup and taking a Malatonin tablit help you fall asleep faster?

Vicky

[RLSmi]

There are no stupid questions.
I don't think the cough syrup would help one fall asleep, at least at the very small doses that I take.
A single dose of melatonin probably would not either. Melatonin apparently is helpful in resetting our circadian "clock" in the case of jet lag.
It worked for me last Spring when I travelled to Greece, Turkey and Israel, especially on the return to the US from Israel.
I continued taking the DM syrup through that time and did not notice any effect of combining DM and melatonin.

Robert

[reverett123]

How's your experiment going?
-Rick

[stevem53]

Hi Rick..This has been a bad week to take notes..I came down with a real bad stomach bug on Sunday thats been going around which amounts to a real bad case of Montezuma's Revenge..Im still weak from it and didnt leave the house untill Wednesday..(yesterday)....But throughout it all I still had more movement ability than I had before I began the DM regimen, except for last night..I felt well enough to get out of the house and I got so carried away with household chores etc that I neglected because of the sickness, that I completely forgot to take my meds at 2:00 in the afternoon..I took a nap at 4:00, and got up at around 6:00, and went and reached for my bathrobe with my bad arm so that I could hit the shower, and the arm was stiff, and I realized why, so I went and grabbed my daily med container, and there were Wednesday afternoons meds still in it..Actually I noticed a difference when I was getting out of bed..I felt like I had broken the chain, and the meds didnt rescue me..I was stiff and weak last night..Today I went out grocery shopping and picked up my income taxes, and rested for the remainder of the day..I am still weak from that stomach bug, but my movements are reasonably fluid today..Ive noticed that I can screw and unscrew a soda bottle cap with much more ease than before I started taking the DM..Basically Ive been resting all week because I was so sick Sunday and Monday I fear relapse..I would honestly say that inspite of being sick all week my pd symptoms werent as bad as they probably would have been otherwise

Steve

[BEMM]

DM must work remarkably quickly if it helped you in spite of the stomach flu, Steve. Most of what you ate and drank must have rushed right through you while you were sick, but the DM was absorbed and effectve, and that is very impressive.
I am going to try it, it sounds very promising - especially promising to me is that it also improved your balance.
Many thanks to all in this thread for yet another possible medicine that is easily found, readily available, inexpensive and potentially really helpful.

birte

[stevem53]

Its certainly worth a shot Birtie..I did something this morning that I havent done in a very long time..I slipped both feet into my slippers without touching them with my hands..and without a struggle..This was near imposible with my right foot for a long time

Be sure to check out the Dextromethorphan precautions

[ashleyk]

I've gone back and read about dextromethorphan and naltrexone, which I take as low dose naltrexone or LDN, and was surprised to learn that they are both dopamine agonists like Mirapex which I also take. My reason for taking naltrexone, off label, for the past 32 months is to hopefully slow or halt PD progression. I can't say I have seen the movement benefit that Steve has seen because I wasn't looking for it when I first began LDN (maybe I saw an improvement in balance). I can say that I don't seem to have progressed but I don't know why. The point of taking either of these drugs (opioid receptor agonists) at a low dose, is to slow or halt progression.
The research done by Dr. Zagon and Dr. Hong emphasize that somehow these opioid drugs work within a low dose window and that to exceed the dose level could make the disease worse. Dr. Hong believes PD is the result of activated microglia cells which cause inflamation and the loss off dopamine cells (he has shown that femtomolar doses of naloxone protect rodent brains against this inflamation). So in the case of naltrexone, which has been used daily at doses of 50 to 100mg for substance abuse, it would not be a good idea to take a 50mg pill for PD (LDN has to be compounded as 4.5mg capsule).
If there is a doctor here or neurologist, are you aware that the drugs mentioned above are dopamine agonists like Mirapex and have they been used to treat PD? These are pretty inexpensive drugs compared to Mirapex. Do you have any comment on the use of these drugs at a low dose to slow PD progression other than not to take them? People mention liver damage but so far there has been no news of people on LDN or DM having this problem at these levels.
Ashley

dopamine agonist definition:
http://www.parkinsonsdisease.com/pcp/PCP7D.HTM

naltrexone: note, can be Rx by doctor, Revia, if you have a substance abuse problem and then you can make you own LDN.
http://www.intelihealth.com/IH/ihtIH/WSIHW000/8124/21291/339954.html
Naltrexone has been used for the treatment of alcoholism since its 1994 approval by the federal Food and Drug Administration. Naltrexone acts as an opioid antagonist within the opioid neurotransmitter system, which is a part of the brain's reward system. When opioids are stimulated, levels of a neurotransmitter called dopamine are increased. Dopamine activity is thought to be key to experiencing the "high" of a variety of different drugs, including alcohol. Naltrexone achieves its effects by "blocking" this domino-type chain of events that lead to the desire to continue drinking. In short, naltrexone decreases the rewarding effects of drinking and reduces the craving for alcohol that often leads people to relapse.

[reverett123]

Sorry about the formatting. Notice that there is research back 15 years.:) :(

1: Zhang W, Shin EJ, Wang T, Lee PH, Pang H, Wie MB, Kim WK, Kim SJ, Huang WH, Wang Y, Zhang W, Hong JS, Kim HC. Related Articles, Links
Abstract 3-Hydroxymorphinan, a metabolite of dextromethorphan, protects nigrostriatal pathway against MPTP-elicited damage both in vivo and in vitro.
FASEB J. 2006 Dec;20(14):2496-511.
PMID: 17142799 [PubMed - indexed for MEDLINE]
2: Li G, Cui G, Tzeng NS, Wei SJ, Wang T, Block ML, Hong JS. Related Articles, Links
Free Full Text Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage.
FASEB J. 2005 Apr;19(6):489-96.
PMID: 15790998 [PubMed - indexed for MEDLINE]
3: Zhang W, Qin L, Wang T, Wei SJ, Gao HM, Liu J, Wilson B, Liu B, Zhang W, Kim HC, Hong JS. Related Articles, Links
Free Full Text 3-hydroxymorphinan is neurotrophic to dopaminergic neurons and is also neuroprotective against LPS-induced neurotoxicity.
FASEB J. 2005 Mar;19(3):395-7. Epub 2004 Dec 13.
PMID: 15596482 [PubMed - indexed for MEDLINE]
4: Zhang W, Wang T, Qin L, Gao HM, Wilson B, Ali SF, Zhang W, Hong JS, Liu B. Related Articles, Links
Free Full Text Neuroprotective effect of dextromethorphan in the MPTP Parkinson's disease model: role of NADPH oxidase.
FASEB J. 2004 Mar;18(3):589-91. Epub 2004 Jan 20.
PMID: 14734632 [PubMed - indexed for MEDLINE]
5: Liu Y, Qin L, Li G, Zhang W, An L, Liu B, Hong JS. Related Articles, Links
Free Full Text Dextromethorphan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation.
J Pharmacol Exp Ther. 2003 Apr;305(1):212-8.
PMID: 12649371 [PubMed - indexed for MEDLINE]
6: Palmer GC. Related Articles, Links
Abstract Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies.
Curr Drug Targets. 2001 Sep;2(3):241-71. Review.
PMID: 11554551 [PubMed - indexed for MEDLINE]
7: Chase TN, Oh JD, Konitsiotis S. Related Articles, Links
Abstract Antiparkinsonian and antidyskinetic activity of drugs targeting central glutamatergic mechanisms.
J Neurol. 2000 Apr;247 Suppl 2:II36-42. Review.
PMID: 10991664 [PubMed - indexed for MEDLINE]
8: Verhagen Metman L, Del Dotto P, Blanchet PJ, van den Munckhof P, Chase TN. Related Articles, Links
Abstract Blockade of glutamatergic transmission as treatment for dyskinesias and motor fluctuations in Parkinson's disease.
Amino Acids. 1998;14(1-3):75-82.
PMID: 9871445 [PubMed - indexed for MEDLINE]
9: Verhagen Metman L, Del Dotto P, Natte R, van den Munckhof P, Chase TN. Related Articles, Links
Abstract Dextromethorphan improves levodopa-induced dyskinesias in Parkinson's disease.
Neurology. 1998 Jul;51(1):203-6.
PMID: 9674803 [PubMed - indexed for MEDLINE]
10: Verhagen Metman L, Blanchet PJ, van den Munckhof P, Del Dotto P, Natte R, Chase TN. Related Articles, Links
Abstract A trial of dextromethorphan in parkinsonian patients with motor response complications.
Mov Disord. 1998 May;13(3):414-7.
PMID: 9613730 [PubMed - indexed for MEDLINE]
11: Montastruc JL, Rascol O, Senard JM. Related Articles, Links
Abstract Glutamate antagonists and Parkinson's disease: a review of clinical data.
Neurosci Biobehav Rev. 1997 Jul;21(4):477-80. Review.
PMID: 9195605 [PubMed - indexed for MEDLINE]
12: Kaur S, Starr MS. Related Articles, Links
Abstract Antiparkinsonian action of dextromethorphan in the reserpine-treated mouse.
Eur J Pharmacol. 1995 Jul 4;280(2):159-66.
PMID: 7589181 [PubMed - indexed for MEDLINE]
13: Montastruc JL, Fabre N, Rascol O, Senard JM, Blin O. Related Articles, Links
No abstract N-methyl-D-aspartate (NMDA) antagonist and Parkinson's disease: a pilot study with dextromethorphan.
Mov Disord. 1994 Mar;9(2):242-3. No abstract available.
PMID: 8196695 [PubMed - indexed for MEDLINE]
14: Bonuccelli U, Del Dotto P, Piccini P, Behge F, Corsini GU, Muratorio A. Related Articles, Links
No abstract Dextromethorphan and parkinsonism.
Lancet. 1992 Jul 4;340(8810):53. No abstract available.
PMID: 1351627 [PubMed - indexed for MEDLINE]

[stevem53]

The only rational basis that I can think of for my symptomatic relief so far is this..Robert and yourself have had pd for appox the same amount of time as myself..You began LDN about 2.5 years ago, as did Robert with the DM..(2 yrs ago)....If we were to play the devils advocate and assume that both of your progressions have been halted as the study suggests..or if it has slowed the progressions or masked your symptoms, or a combination of the above..and myself on the other hand..I definately have 2 years of uninterrupted progression..I have more symptoms to treat, keeping in mind that you both were in the early stages of pd when you began the LDN/DM regimen..Then again it could be that you are both in fact on the Sinamet honeymoon and I am merely enjoying the dopamine reuptake inhibitor consequences of DM..I think now that a few more folks in our community are interested in trying DM we will know one thing for sure..We still wont know for a number of years if it has halted our progressions but we will have some comparisons on symptoms

[reverett123]

First of all, there is more than one effect here. Symptomatic relief for Steve is a short term effect. Protection against further degeneration by quieting the immune system may be the case for Robert.

An additional possibility is endocrine effects on the HPA axis stress response resulting in Steve's sense calm at the podium.

Taking a "Multihit" viewpoint, these may be three entirely separate effects acting via independent mechanisms. And one or more may be dose dependent and there is a 50% spread between Steve and Robert. With endocrine affairs a little goes a long way as well.

Leaving Ashley out for now and just talking to the DM crew, have either of you tried either lower or larger doses?

And have either of you tried taking it at a different time of day?

-Rick


The only rational basis that I can think of for my symptomatic relief so far is this..Robert and yourself have had pd for appox the same amount of time as myself..You began LDN about 2.5 years ago, as did Robert with the DM..(2 yrs ago)....If we were to play the devils advocate and assume that both of your progressions have been halted as the study suggests..or if it has slowed the progressions or masked your symptoms, or a combination of the above..and myself on the other hand..I definately have 2 years of uninterrupted progression..I have more symptoms to treat, keeping in mind that you both were in the early stages of pd when you began the LDN/DM regimen..Then again it could be that you are both in fact on the Sinamet honeymoon and I am merely enjoying the dopamine reuptake inhibitor consequences of DM..I think now that a few more folks in our community are interested in trying DM we will know one thing for sure..We still wont know for a number of years if it has halted our progressions but we will have some comparisons on symptoms

[reverett123]

:)
You seem to be doing well and are stable, so maybe you should be our "control" for now. Another week to let the MAO wash out and I will start low but then inch up a little above you to see what happens. So long as there are so few of us we can take it slow and easy. I did buy some of the local pharmacy's finest today. Did you know they had it in the five gallon size? :D

[stevem53]

Bucket o' DM..Wonder what the street value is?..:D ..At 1/2 teaspoon per night that should last me for the rest of my life..:D

It will be interesting to compare results

[mrsD]

There are other forms of DM you can use.

Delsym is pure DM in sustained release dosage form. Most pharmacies carry
it:
http://www.delsym.com/

Some people get nausea from the guaifenesin in Robitussin DM. So if you prefer single dose DM the Delsym is for you. But it costs more.

There are tablets also, with guaifenesin and DM 30mg sustained acting:
Mucinex DM
http://www.mucinex.com/pdf/Mucinex_DM.pdf
Some stores now have a generic available for this.

Kids abuse DM so if you begin to use it in high amounts, you may attract
attention in the store. Some pharmacies may have it behind the counter because of this. Coricidin HBR recently was targeted by abusers and is
often behind the counter now.

Very high dosing of DM can cause dissociative CNS symptoms and a peculiar
"buzz"...but in the doses mentioned here, that should not be a problem.

Here is more information:
http://www.nhtsa.dot.gov/PEOPLE/injury/research/job185drugs/dextromethorphan.htm
Drug Interactions: Should not be taken with Monoamine Oxide Inhibitors (MAOIs) and Selective Serotonin Reuptake Inhibitors (SSRIs) because of an apparent serotonin syndrome (fever, hypertension, arrhythmias). Should be used with caution in atopic children due to histamine release. Additive CNS depressant effects when co-administered with alcohol, antihistamines, psychotropics, and other CNS depressant drugs.

The serotonin reuptake is documented, but not common.

This is also interesting:
Pharmacodynamics: Dextromethorphan acts centrally to elevate the threshold for coughing, and has no significant analgesic or sedative properties at antitussive doses. It is proposed that dextromethorphan is a glutamate and NMDA antagonist, and blocks the dopamine reuptake site. It may also increase 5HT 1A activity possibly via NMDA antagonism.

[RLSmi]

MRSD, Delsym and some other long acting DM (aka DXM) preparations also contain polystiril, a substance that slows down the absorption of the drug. I was told by someone who is actively doing research on this class of drugs that using the long acting forms will defeat production of the "spike" of concentration of DM produced by the mini-dose that is needed.

Also, the time it is taken, just before bedtime, is important for producing a brief blocking of the opioid receptors just before the natural period of release of endorphins (2 to 4 am) the hormones that are beneficial in calming the over-active microglial cells in the PD midbrain. Too much drug, or taken at the wrong time, may cause prolongned receptor inhibition, or inhibition at a sub-optimal time for taking advantage of boosting the normal endorphin release.

This is my opinion, based on what I have learned from other scientists who have studied the process extensively in the laboratory for the last ten or twelve years.

Robert

[reverett123]

You brought up a good point about the psychological risks of habituation for those of us with the right personalities. The taste and the fact that it is a liquid, etc. When I was at CVS yesterday I also picked up the gel cap form as well for portability. You would lose the dose control (they're 15 mg) but it is a possibility to remember. Thank gawd you can't smoke it. ...can you? :D

[ashleyk]

Over the past week, all this discussion on DM has caused me to search the web for more info after I learned that DM and LDN are dopamine agonists as well as opioid agonists. According to the people who have done the research on DM and LDN (Dr's Bihari, Zagon, Hong), these drugs are neuro protective at very low doses, to use them at high doses negates their effectivness or worse.

My question is, would Mirapex at it's normal dosage override or defeat the low dose protection of DM or LDN since it is also a dopamine agonist? I did a search on "Pramipexole (mirapex) opioid antagonists" and did not come up with a match (that's good?) since I think DM and LDN work thru the opioid receptors for neuro protection. Since I take Mirapex, I wonder if it effects or negates the LDN I also take. If anyone works in this area, your comment would be appreciated.

As far as DM being addictive at only a half or one teaspoon a day, I'd be very surprised. I wouldn't think you'd feel a thing. In this case, a small dose is better then a big one.
Ashley

[reverett123]

I mentioned this question about DM and PD to Anne Frobert, the French MD and PWP who posted a few times on banding. She pointed out that levodopa has at least two effects. One is short term and helps us move. The other longterm one is dangerous and leaves us damaged.

It is possible that a similar dual action (thought hopefully with a better outcome) is at work here. What I mean is that the benefits that Steve is experiencing may be totally unrelated to what Robert is observing and I suppose that Dr. Hong could be looking at a third process. Short term symptom relief is something we can readily observe. Longterm effects, both good and bad, are beyond our capabilities to evaluate.

Something just wafted across my brain as I was thinking about the possibility of the higher dosage required for one negating the the other. There was something, and I think it was curcumin, that was effective at lower doses but lost some of its benefits as dosage increased. It might be acting on the same systems.

[made it up]

Hi Reverett,
Do you have a certain time when the one legged thingy is done?
The fluctuations in a PWP are many.... off, dyskinesic and of course on, a nice on.
What I'm getting at is how can you know its not the prescribed levodopa doing its job when you can stay on one leg longer but the cough syrup?
Regards,
Lee

[reverett123]

why, it's almost a zen koan :)

i do it in mid-afternoon when i am at my best. my goal is to detect change so the most important thing is consistency.

rick

[stevem53]

A short update:..

Now that Im over the stomach bug, and the weather is warmer, Ive been getting out of the house and working on the 19' fiberglass boat I recently bought..Ive been setting it up to haul my conch traps, and have it in my yard on a trailer..I mustve climbed in and out of it atleast 25 times in a 3 1/2 hour period today..I was fatigued after I got done tinkering as usual..but climbing in and out that amount of times wasnt as big a deal as it was last year at this time when I was working on the other boat that I recently sold..The last few times I had some trouble lifting my bad leg up high enough getting in and out..I took and hour and a half nap and went out to the store tonight, and much to my surprise I had no trouble putting my coat on or getting my arms behind my back to grab the sleeves to take it off..My balance is still better than usual, and stiffness still improved..What I have been curious about was how I would fare after doing some work, and what Ive noticed is that afterward I still get fatigued, but after a nap Im in reasonable shape again, and seem to maintain some additional movement and balance..I definately feel like Ive done some work today, but Im not all parkied out like I was feeling before adding DM to my daily regimen

[burckle]

Robert:

I looked up Simply Cough on he web and got this warning.

Lloyd

WARNINGS
Do not use in a child who is taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric or emotional conditions, or Parkinson's disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your child's prescription drug contains an MAOI, ask a doctor or pharmacist before giving this product.

[RLSmi]

Robert:

I looked up Simply Cough on he web and got this warning.

Lloyd

WARNINGS
Do not use in a child who is taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric or emotional conditions, or Parkinson's disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your child's prescription drug contains an MAOI, ask a doctor or pharmacist before giving this product.

All of the dextromethorphan-containing cough preparations I have seen have that warning. It should certainly be heeded, regardless of whether the one taking it is a child or adult.
It is my opinion that, at the very small doses I and others are taking for the purpose of neuroprotection (5-8mg per night) any interaction with almost any other drug would be negliglible.

Remember that the dosage recommended for cough supression on the bottle is several times higher, and allowed at 6 to 8 hour intervals.

As I have posted before several times, I am not recommending that anyone else embark on the experimental use of this drug for PD neuroprotection. However, when someone asks me what I am taking, I give the most complete answer I can.

Robert

[EnglishCountryDancer]

I looked very carefully at the cough medicine Benylin(dry coughs )which contain Dextromethorphan hydrobromide 6.5 mg per teaspoon and could find no warning against its use by P.W.P.Yes, all the other warnings but no mention of Parkinson's.

[EnglishCountryDancer]

Whoops .I misread the post.Yes. there are warnings about which drugs you should not use it with and one is a drug sometimes used for Parkinson's.

[stevem53]

I am taking approx 7.5 mg or less per night..(1/2 teaspoon @ 15 mg per teaspoon)

I am not recommending this to anyone

From Wikipedia

Dextromethorphan should not be taken with any of the following:

monoamine oxidase inhibitors (MAOIs)[5]
selective serotonin reuptake inhibitors (SSRIs)[5]
CNS depressant drugs and substances, including alcohol, antihistamines, and psychotropics, will have a cumulative CNS depressant effect if taken with dextromethorphan.[5]

From medicine plus:..

http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682492.html

From:..Drugs and Human Performance FACT SHEETS -

http://www.nhtsa.dot.gov/people/injury/research/job185drugs/dextromethorphan.htm


From:..DEXTROMETHORPHAN (Street Names: DXM, CCC, Triple C, Skittles, Robo ...

http://www.deadiversion.usdoj.gov/drugs_concern/dextro_m/dextro_m.htm

From:..Dextromethorphan (PIM 179)rom:..

http://www.inchem.org/documents/pims/pharm/pim179.htm

From:..Consumer Reports Medical Guide -

http://www.consumerreports.org/mg/drug-reports/dextromethorphan.htm

[ashleyk]

Hi, I did a quick search and this is the first item I came across. There was a clincal trial using DM to treat advanced PD patients at the NIH about 10 years ago. The DM dose used in the trial was 10 to 20 times what is probably recommended for PD neuroprotecion. Again, the purpose of low dose DM or naltrxone is neuroprotection. Has anyone found a reason why DM is counter indicated for PD?
Ashley

http://clinicaltrials.gov/ct/show/NCT00001365
The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60-120 mg/day). The 12 remaining patients either experienced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double-blind, placebo-controlled, crossover study with two 2-week arms separated by 1 week wash-out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% according to UPDRS interviews, without compromising the anti-Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa-associated motor complications.

[reverett123]

...you still doing well? It has been two weeks since my last MAOI so I am going to edge into the deeper water a bit. I am going to work my way up to a single 15 mg gel cap. I know that is higher than the doses we've been talking about but the advantages of having the option of the handy capsule are considerable and the dose is still very reasonable if one is a non-Parkie.

It is important to note that I am looking for short term relief of symptoms whereas Robert's approach is directed at long term protection. The two may or may not be compatible.

I guess it would be a bit melodramatic to don a WW1 flight cap and goggles at this point...:)

[stevem53]

Rick..Im still feeling above average for 17 days in a row

[reverett123]

It is 9:00 AM and I am twelve hours in, having started with a 7.5 mg dose last night. Observations to date:
1) Stayed up until midnight as usual but went to bed without my "normal" level of symptoms. Was in pretty good shape, actually. Rare for me but not at all unheard of.
2) Slept very well. One trip to the loo which I consider a pretty good night.
3) Up at 7:30 AM and seemed better than usual by about a 25% factor for function.
4) Am holding to my regular meds. Turned "on" in the usual 45 min to 1 hour for me. Seem normal response in other aspects
5) I notice that I am unusually handsome today. :D

[RLSmi]

It is 9:00 AM and I am twelve hours in, having started with a 7.5 mg dose last night. Observations to date:
1) Stayed up until midnight as usual but went to bed without my "normal" level of symptoms. Was in pretty good shape, actually. Rare for me but not at all unheard of.
2) Slept very well. One trip to the loo which I consider a pretty good night.
3) Up at 7:30 AM and seemed better than usual by about a 25% factor for function.
4) Am holding to my regular meds. Turned "on" in the usual 45 min to 1 hour for me. Seem normal response in other aspects
5) I notice that I am unusually handsome today. :D

Handsome to another white rat, is suppose!

[stevem53]

Although yesterday was an above average day, it wasnt quite as good as the previous days

Today is still above average but my legs are working better than my arms..balance is good

One of the motor skill tests that my Dr does is the doorknob turning..arms extended..twist hands back an forth..Prior to DM I could perfom this task with my left hand without a problem, but my right hand would make about an eighth turn to and fro and shake..My right hand and arm is my worse pd disability..For the past 17 days with the exception of this morning I could do the doorknob turning with my right hand at about 60% efficiency or a little better from day to day..Today however it is back to square one with that, and my left hand is a little bit slower as well..Today I can still get up out of a chair with ease instead of taking three steps backward as the chair slides behind me when I attempt to stand up an balance..Some chairs are easier to get out of than others depending on their weight..My kitchen chairs tend to slide backward as I rise, and this is what use as a gague..I have been able to get up without the chair sliding backward consistantly..There are a bunch of little things Ive noticed that have improved

The "HANDSOME" I have experienced however turns out to be a hallucination..:D

[reverett123]

:)
This is the Bible Belt and we don't cross species. Despite what you might have heard. :)

A couple of other observations while I'm here:

1) Belly bloat (or abdominal distension if you wish) is noticeably low this morning and confirmed by my wife
2) muscle tone is better than usual

-Rick

[reverett123]

Steve-

It might be a good idea to skip a day from time to time, especially if we are dealing with receptors. They might need a break to "reset" or something.

For my own self, it is positive for the most part but with a few suspect elements.

The latter: 1) It took me over an hour to turn on this morning. A little more than usual but not much. 2) Yesterday afternoon went off for a couple of hours but I had good cause. Trying to install a most uncooperative new router and took it personal after the third hour of trying. :D
3) Awakening dystonia of left foot slightly worse than usual this morning.
On the plus side: 1) Slept well again, but during a brief wake up I discovered that I was able to turn in bed like old times! 2) No offs today at all. 3) Skipped my last meds of day last night without serious problems. 4) General feeling of better health. Can't really explain that.

There is, however, one thing in particular that may be important but will need a little explaining. I play around with some basic biofeedback and have sensors that record, among other things, heart rate variability. I won't bother to explain HRV since it is easy to look it up, other than to say that a certain wave form is a sign of good cardiac health and the further you deviate from it the less your chances of surviving a heart attack. It involves the autonomic nervous system and also the vagal nerve.

Now. I didn't want to alarm myself but since I began checking it a year ago my HRV was so bad that it was almost a flat line! Not good. I know what other people showed on the same equipment but just wrote it off to the PD damage and hoped for the best.

Today I experimented and found that for the first time I showed an HRV wave that was near normal! I have no idea what it means. Perhaps the vagus nerve is nudged back to life or something. But if any "real" researchers are lurking, please make note.

In fact, I will attach a jpeg of the various outputs. At "t+0" I had had no DM for 12 hours. The green line is the HRV and is almost non-existent at t+0.

[stevem53]

The past three days Ive been backsliding a little bit everyday..Ive been out working on my boat in the yard here..I could blame that on the fact that Im not feeling as good, but during the last warming trend in the weather last week I was doing more work then than I am this week..so I cant blame added activity on this..Seems with pd there are somethings that work for a while but it always seems to bring you back to square one..Both arms are weak today and my bad arm/hand is uncoordinated again..My gait is still above average, and so is my balance..but feeling kinda sluggish..Fatigue hasnt been as bad, and am taking an afternoon nap whether or not the fatigue has set in yet or not..My short term memory seems to have improved a bit..All in all my condition is still above average, but not as good as it was last weekend and at the beginning of this week..A big improvement nonetheless over what it was prior to taking DM..Before taking DM I was getting very uncoordinated, balance was getting worse, and had some near falls but I am still strong enough to right myself and regain my balance..I had this overall feeling which I can only explain by saying that it felt more like pd was in control than I was, and now I feel like Ive gained some ground back

I have no idea what that heart monitor is all about..lol..I'll have to google it

[AnnT2]

From what I have read, this over the counter drug can be addictive. My sister's drug of choice at 19 was an over the counter cough syrup. She would become drunk and incapacitated beyond belief when she took it. She was a full-fledged alcoholic by the age of 20, and limped through life never really able to be free of addiction. Was it her make-up? Was it the cough syrups' effect on her? Was it both? I know the dosage is small, but if it feels really, really good, would one be able to stay at that dose? One of the last things she did before commiting suicide at age 60 was to drink. This column brings back a certain feeling of terror. Be very, very cautious that you don't substitute one disease with another.

Ann

[mrsD]

is not addictive.

It is not to be confused with other OTC cough preparations containing
codeine. These used to be favorites for kids/teens. Most states have cracked
down on OTC sales of these exempt narcotics...requiring signing a book, with ID and no more than 4 oz every 48 hrs. Terpin hydrate with codeine is no longer even manufactured...this was the highest alcohol containing product out there, at 40 proof.

The small amount of DM discussed here is certainly not in that league!

The DM abuse now is new, and quite different.
The guaifenesin in the DM mixtures now, causes vomiting before the high typically, so drinking a whole bottle, is not likely.

[stevem53]

Thanks for your concern Ann..I have a history of addiction, and I completely understand what your sister went through..Was it her make-up or the effects of the cough syrup?..From my experience I would have to say it was make-up..then effect..ie finding a drug of choice..Unfortunalely those who dont recover face the risk of death either through suicide, over dose, or organ failure due to addiction/alcoholism..and I am sorry to hear about what happened to your sister..that is sad..I of all people have to be extra careful..I have a healthy respect for narcodics etc, I have to..There have been a few times where I have had medical procedures that required narcodics..colonoscopy/andoscopy, and had to take valium to redo an MRI at the time of dx with pd because I was so uncomfortable laying in the tube for 2 hours that they had to sedate me, and I had to pick up the prescription for the valium..the Rx was for 2 valium..CVS gave me 10 which is the minimum order, so when I got home the first thing I did was to flush 8 of them down the toilet..immediately..The first few times I took the cough medicine I knew that it had the potential to be abused, I could taste it..but now after about 3 weeks it just tastes like candy flavored water..I went through the same thing with mouthwash 17 years ago when I got out of rehab..I had to rid the house of mouthwash for a few years..Now I use it and never think about it anymore..The first time I used it after getting out of rehab it scared me because I could taste the alcohol in it..It has been told to me by countless people that if I am faced with a situation where I get an Rx for narcodics, that as long as I take them as prescribed then it is medicine..and anything more than that becomes abuse, and recreation

[KC Tower]

There are DM cough medicines that are alcohol free.

,,, ken

[BEMM]

I bought a bottle of Robitussin for adults, and took the first 1/4 spoonful this morning. Thought I would start with even less than 1/2 tsp a day, to see if so little would be of any help at all.
But what an awful, disgusting taste! I can hardly get the 1/4 tsp down. I will keep it up until this first bottle is empty, and if it has had no effect by then, my taste buds will be grateful. But if it helps me it is certainly well worth the taste jolt.

white rat birte

[reverett123]

...about this blasted time change so will be brief-

Good day yesterday. So good that I forgot end of day meds and cough syrup until nearly bedtime. Decided not to take either and see.

Biggest difference in night was back to usual difficulty in turning in bed.

Also, yesterday morning I noticed my early morning lower back ache was gone. Still gone todat.

Now M U S T H A V E C O F F E E !

[BEMM]

Well......I took my 1/4 tsp Robitussin this morning of my second day as a white rat, and today I have been able to get up from sofas and chairs with hardly a struggle. I have not been able to stand up from sitting without a huge struggle, or without a helping hand, for the last three, four years.
I can't believe that it could be placebo effect, but two times of 1/4 tsp Robitussin could not possibly help so much so quickly.
It must be a fluke, and tomorrow I will have to be hauled out of chairs and sofas again.
But you can be sure that I will continue taking Robitussin.

birte

[stevem53]

I had the same kinds of experiences..Who would have thought?..I had a good day today..no fatigue for a change..I laid down for an hour and a half but didnt sleep..Its 11:00 pm and Im still going strong..I think what causes the surge is that DM is a dopamine reuptake inhibitor, and as I said before I suspect that it helps the Sinamet work more efficiently..Strange..Very strange..:confused: :D

[reverett123]

I find myself doing well enough that I am forgetting to take my meds on schedule. I've got to get more disciplined or I'll be worthless as a Rat.

Big effect noticed when I roll in bed. I can. :)

[RLSmi]

Haven't heard from you in the last few days. Are you experiencing anything different?
Robert

[caya]

Hi:

YES,YES,YES!!!! I started my bedtime DM on March 4th and was going to wait until the end of the month to give y'all a report. However, I guess this would be a good time to share a progress report. My biggest problems and main symptoms are my voice and internal tremors. The voice trouble has been complicated by enormous amounts of mucus down deep in my throat and on my voice box. Nothing the docs have given me so far has worked. I work in sales and virtually not being able to talk has just about done me in.

Well, I am here to tell you the muscus problem is all but gone. I no longer feel like a cat with a hairball !!! My voice volumn is still a bit low but I can deal with that. Being choked and unable to hardly speak with all the mucus is what was making me nuts.

I have never had the typical PD "resting" tremor. I have always had what I call internal tremors. You know how you feel when you get real cold and you shiver and shake internally from head to toe? That is my tremor situation......and believe me, when it is really bad it is absolutely debilitating. Since being on the MD, my internal tremors have virtually stopped !!! I got very upset about somethings last week and then again yesterday and both times trembled a little but it only lasted a few minutes.

Soooooo at this point, the MD has addressed my two main PD issues. Don't know how long it going to last but until something breaks loose or comes untied, I AM SOING TO STAY ON IT !!!!!!!!!

CAYA

[stevem53]

Another satisfied customer..:D

[RLSmi]

of your positive results, Caya. I definitely think DM has a place in improving PD. As we all know, however, it will be years before anything definite can be said about it slowing or arresting progression.

[reverett123]

My experience is still positive, but I did run across one study using DM for ALS that found that about ten percent of the population are what are called "slow metabolizers" of DM. The bottom line is that the slow metabolizers build up levels of DM in the system quicker and with far less needed than normals. So, if I were experimenting I would start slow and build up over several days. Then, once I had reached what I thought was where I wanted to be I would back off a little until I noticed the benefits dropping. Then inch up a little. That would be a way for me to account for my individual metabolism. The stuff seems pretty safe but the differences in serum levels for slow metabolizers was as high as a factor of ten so you could be taking more than intended in that case. Might still be safe but prudence is called for.

[virginia mcintyre]

Hello, everyone...I have been visiting this site for quite some time, now, and finally decided to join the group. However, I was unable to respond to the "invitation" to introduce myself...and so, I will briefly tell you, here. I will "confess" that I am not a pwp, but, rather, I am a caregiver to a pwp who was diagnosed in 1998, although in retrospect, it is probable that she had PD several years before diagnosis. Why am I here?... you may ask...and, the answer to this is that I have, as you might well imagine, read and researched this disease from the very beginning of my pwp's diagnosis, but it has been my experience that those who are afflicted with this disease are the "most experienced"and from my perspective, I believe that I will be able to learn so much from you...to become a better educated caregiver.

I have been fascinated by the topic that many of you have been discussing, i.e., Dextromethorphan (DM) and its potential benefits for pwp's. Ironically enough...just recently...my pwp had an upper respiratory infection accompanied by a very deep, hacking cough. However, it seemed to be the consensus of the pharmacists that we consulted that she should avoid the DM, although I had read that it was only contraindicated with the MOAI's which my pwp is not taking. She is taking Sinemet and Comtan. In fact, she consulted her neurologist who also said that she couldn't take ANY cough medicine! Then, I happened to read this thread about DM and its possible BENEFITS to pwp's. It all just seemed so ironic that on "one side of the coin", DM is taboo...while, on the "other side of that coin"is the very positive information...and the extemely positive experiences of some of you, here.

I hope not to be considered an "outsider"because I, myself, do not have PD. I am here to learn from those I consider to be the "experts"...the experienced...and it just may be that I may be of some help to you as well.

I will say that I belong to a Caregiver's Forum where I have learned a great deal, i.e., from the Caregiver's perspective...but, I am happy to be here with all of you who will enlighten me from the perspective of one who is afflicted with this disease.

Virginia

[rd42]

Everybodies welcome here. :)

[stevem53]

Did the Neurologist/Pharmasist give you any explanation for their taboo of DM?

[virginia mcintyre]

Thank you, Steve, for your "welcome". No...neither the neurologist nor the pharmacists gave an explanation as to the DM being taboo. I believe that they may be so engrained with the contraindication of DM w/the MAOI's w/no thought being given to the fact that my pwp is NOT taking an MAIO...even the neurologists sometimes seem to be oblivious. I certainly plan to discuss this with my pwp's neurologist at her next visit..she sees him every 3 months...and speaks with him almost weekly, especially if/when "tweaking"/changing meds, etc. I will also mention what the experience has been of those of you, here. I have really read your posts about this with so much interest, Steve. I want to ask you. Were you at BrainTalk Communities at one time? I My pwp was registered, there, and I use to read the posts there from time to time. I am really not certain about my registation, here...I noted with my first post that I was "listed" as a visitor...but, I did register here...I was just not able to find the "new member" place where I was invited to introduce myself. I am not exactly a computer "whiz"...and sometimes, I find it difficult to navigate the system.

Thank you again, Steve, for welcoming me.

Virginia

[stevem53]

I still post at Braintalk..Braintalk had a major crash last summer and was down for a few months..Dr John who is the Administrator of this site was kind enough to develop this website so that we would have a place to keep in touch..It was originally set up a temporary meeting place in the interum of the absence of Braintalk, by was made permenant by popular demand

I would be interested about what you pwp's Dr has to offer on this subject

[virginia mcintyre]

Steve...I will let you know what the neurologist says about the DM when we visit him..I believe at the end of this month. It has been my experience that the doctors...neurologists...are learning from pwp's and their caregivers. Our internist has told us that he had learned so much from us...and even the neurologist was not aware of the obsessive/compulsive aspect of Mirapex until we brought it to his attention. It was just shortly after we mentioned it to him that this particular side effect of Mirapex became apparent.

My pwp use to post at BrainTalk occasionally...Doreen...you may or may not remember her. It was through BrainTalk that we met Scott and Cera (you probably remember this very nice couple). We became very close cyber friends and are in touch regularly. I can remember some others, too...Toad, Jaye, Greg, Birte, Textetu (sp?)...Paula..Thelma...just some that I remember having seen when we use to go to BrainTalk...sometimes to post (i.e., Doreen would post)...and I was just a "lurker"!!! I am happy to be here, now, as a registered member of NeuroTalk. Yours is a name that is very familiar to me so that I almost feel that I know you.

Who knows, Steve...it just may be someone not at all associated with the medical profession or the pharmaceutical arena that will, ultimately, find the cure! This may seem far-fetched, but it definitely is not beyond the realm of possibility as I see it.

Virginia

[reverett123]

I'm still doing pretty well with the DM but had a rough day. Turned "off" three times. I blame it on having had a bad night's sleep but in casting about for other explanations I came across the fact that green tea is a weak MAO inhibitor. I don't think it is anything to be worried about but just be aware.

[stevem53]

As I mentioned I had slid backward a few paces this week..So last night I purposely didnt take my daily dose of DM, and today was the worse day Ive had since prior to taking DM..I had some trouble with movement, felt out of sorts like I did before taking DM..and when I have trouble with a task my body wants to try to compensate with body language, something that was new in the past few months, but disappeared when I started DM over 3 weeks ago..There are some disabilities that I revisited today that were gone while I took DM..So it seems to me when I have a bad day it would have been worse without DM..That is my judgement call for now

I wont go to bed without taking it tonight..thats for sure!

[BEMM]

Yesterday I had a not so good day. I was tired and my back hurt. Today I felt almost 'normal' all day, until dinner time, when the usual evening fatigue set in. Today I got up at 6, showered, dressed, and spent some time on the computer before I took my pills, and that not because I was off, but because I always take them with breakfast. The difference between yesterday and today is huge, and that is the nature of PD, with or without DM. We have good days and bad days, sometimes for no reason it seems. I think that no matter how much DM helps, we are still going to have days when PD gets the upper hand.

Courage, white rats, we're not giving in.

birte

[stevem53]

I took my dose of DM before bed last night and I feel great this morning!..Energetic, confident, fluid movement..a huge change from yesterday..I never feel this good, even cooincidentally without DM

[rd42]

Is there a specific brand you guys are using, or just any cough syrup with DM?

[RLSmi]

I think the most important thing to look for in the DM-containing cough preparation is that it contain no additional active ingredient such as guafinesin or polistirex. Also, try to get a pediatric preparation with no more than 7.5 mg / 5 ml (5 ml is one tsp). This makes the small dose of 4-8 mg easier to measure. I prefer the "Simply Cough" which contains 5 mg / ml, but have not been able to find it recently.

The polystirex causes the DM to be slowly released over a period of several hours, and it is apparently important that the small dose "hit" the brain all at once in that critical time a couple of hours before the nightime sleep period when your body normally produces your natural endorphins. Polystirex will prevent this.

Guafinesin is a decongestant, but at the small amount taken probably has little or no effect.

Robert

[Curious]

My pwp use to post at BrainTalk occasionally...Doreen...you may or may not remember her. It was through BrainTalk that we met Scott and Cera (you probably remember this very nice couple). We became very close cyber friends and are in touch regularly. I can remember some others, too...Toad, Jaye, Greg, Birte, Textetu (sp?)...Paula..Thelma...just some that I remember having seen when we use to go to BrainTalk...sometimes to post (i.e., Doreen would post)...and I was just a "lurker"!!! I am happy to be here, now, as a registered member of NeuroTalk. Yours is a name that is very familiar to me so that I almost feel that I know you.



Virginia

this is OT to this thread...but another member has been looking for scott and his wife. me included. :) i used to go to chit chat at mgh and bt with scott and c. please say hello from us. we would love to hear from them.


carry on white rats. :D

[reverett123]

Sorry but there is a problem. Monitor your blood pressure. I just got a reading of 175/105. Not good since I usually run about 140/90.

I'll watch it and let you know. It may vary from person to person too.:mad:

[AnnT2]

Are Amantadine, Sinemet (generic), or Mirapex ok to take with dextromethorphan? Or are they MAO inhibitors?

Ann

[RLSmi]

The most common MAO inhibitors prescribed for PD are Eldepryl (selegiline) and Azilect (rasagiline). Several other MAOIs may be prescribed for a variety of other medical conditions. To be sure, check with your pharmacist about other meds you may be taking.

I left Amantadine off. It is not a MAOI either.

[stevem53]

Sorry but there is a problem. Monitor your blood pressure. I just got a reading of 175/105. Not good since I usually run about 140/90.

I'll watch it and let you know. It may vary from person to person too.:mad:

This is what I found, but claims hypertension is a side effect of a 250-1000 mg dose..My BP runs on average about the same as yours, but havent checked mine lately..I have doubts that 5-8 mg would elevate BP

http://www.nhtsa.dot.gov/people/injury/research/job185drugs/dextromethorphan.htm

Side Effect Profile: Adverse effects with recommended antitussive doses are rare. However, nausea, other gastrointestinal disturbances, slight drowsiness and dizziness can occur. Following acute doses of between 250-1500 mg, the following clinical and overdose symptoms have been reported: excitation, nausea, vomiting, drowsiness, dizziness, blurred vision, nystagmus, dilated pupils, body itching, rash, ataxia, sweating, hot/cold flashes, fever, hypertension, shallow respiration, urinary retention, diarrhea, opisthotonos (spasm where head and heels are bent back, and torso is bent forward), toxic psychosis (hyperactivity, marked visual and auditory hallucinations), coma, and an increase in heart rate, blood pressure and body temperature. Side effects can be serious if very large doses of the combined preparations are ingested; for example, guaifenesin and dextromethorphan can cause severe nausea and vomiting; chlorpheniramine and dextromethorphan can cause seizure, loss of consciousness and bleeding.

[reverett123]

..that it may be an interaction with something else and I'll investigate further. Otherwise I've been impressed with the DM. Also, I do have high BP anyway and am on meds for that, so there may be a factor.

Even with all that, I have awakened at 5:00 AM. taken my meds, and am "on" at just 5:30. Usually there is an hour of thumb twiddling for me in the initial wait.

[mrsD]

but guaifenesin is NOT a decongestant. It is a mucolytic, and does not raise blood pressure. It may cause nausea however. It is often COMBINED with decongestants, so read labels carefully. Guaifenesin is typically used in heart patients and those with hypertension and is safe in that respect.

Also pediatric products contain mixtures of things as a rule, or are also long acting now.
Here is Robitussins new line:
http://www.robitussin.com/formula/index.asp
Robitussin maximum is no longer on the website...but it is still on Drugstore.com:
http://www.drugstore.com/products/prod.asp?pid=11160&catid=11733&trx=PLST-0-SEARCH&trxp1=11733&trxp2=11160&trxp3=1&trxp4=0&btrx=BUY-PLST-0-SEARCH
This does not have guaifenesin in it.

DM interacts with SSRIs too. I posted that earlier in this thread. Not commonly but it does happen. I would expect it at higher doses of both drugs, and/or in slow metabolizers. People with abnormally high levels of serotonin physiologically would be at risk also, these include hidden tumors secreting biogenic amines (lung cancer) or undiagnosed carcinoid syndrome (often hidden and hard to diagnose).

But basically DM is easy to tolerate for most people.

[AnnT2]

After research, reading the posts about good results others have had taking dextromethorphan, and finding a pediatric dose with no alcohol or other active ingredients, I took one/half teaspoon of Robitussin pediatric cough syrup before bedtime. I almost immediately felt a little queasy and one hour later was awake with a dry eye feeling and a rapid, rapid heartbeat. I tried to keep calm, but I kept thinking, "What the heck is this?" This morning I awoke feeling stiffer than ever. Everyone's PD is different, and I guess this medicine is not for me.

Ann

[stevem53]

I tried something different last night..actually by accident..I usually take my last dose of Sinamet for the day at 7:00 pm, and I didnt remember to take it untill 11:30..I took the DM at 12:30, and am having a real good day today, all except for some weakness in my right wrist and forearm

[reverett123]

And since we are often taking different regimens we are even more so. In my case I have had to choose between the DM and some other supplements that have proven valuable and the latter have won out. One of the reasons they work is that some are natural MAO inhibitors and as a result are not compatable with the DM, much to my disappointment.

I don;t know what Steve takes besides his prescribed meds but it may be that DM is a good choice for those who don,t use a lot of other stuff that might react with it.

Steve do you take much other stuff? And what about you Ann? Just looking for patterns.

[stevem53]

I take;..

Sianmet 3x25/100

Mirapex 2x.25

I am definately undermedicated, and should at least take 1 more Sinamet daily

No suppliments, and I dont pay attention to my diet and have taken Sinamet just before or after eating protien or what have you

[AnnT2]

I take anywhere from two 25/100 Sinemet per day to three halves of 25/100. Sinemet makes me grind my teeth, so sometimes I cut it in half. I take one 100 Amatadine per day. Finally, from dinner on I take three .5 Mirapex.

Did anyone else have a rapid heartbeat? I looked up DM and rapid heartbeat and got it as a side effect of overdosing with DM. Was half a tsp. too much?

Ann

[reverett123]

Never thought you'd hear that, did you?:D

but to get serious, Steve is a good example of a standard medication program and that could be why he is doing so well - i.e. no "stealth" MAO inhibitors.

Ann is a tougher guess, but one possibility is the "slow metabolizer" explanation that I mentioned in an earlier post. I forget the exact number but I think five percent of us have a system where a little DM goes a very long way.

So, if those guesses are right, then it would be sensible for someone who didn't want to tackle the "alternative" route to simply do like Steve.

And if someone has a body that doesn't get along with the DM might want to investigate things like green tea extract which offers some of the same protections/

I think there are several lessons here but the big one is that there really can be something important lying right under our noses for years. It is almost a textbook example and I find it encouraging. I nominate Steve for the Big Cheese prize to be shared with Robert, Ashley, Cara, Ann, etc etc :)

[reverett123]

This may be Ann's answer too. Close call.

1: Arzneimittelforschung. 1982;32(10):1241-3.

Effect of 1-aminoadamantanes on the MAO activity in brain, liver, and kidney of
the rat.

Wesemann W, Ekenna O.

In order to elucidate the possible interference of the antiparkinson drug
1-aminoadamantane (D-1, PK Merz) and the antispastic compound
1,3-dimethyl-5-aminoadamantane (DMAA, D-145, memantine, Memantine) on
neurotransmitter metabolism, the effect of D-1 and its C-alkyl derivatives
memantine, 1-amino-3,5,7-trimethyladamantane (D-191), and
1-amino-3-(n)-butyladamantane (D-178) on MAO activity in brain, liver, and
kidney of the rat was investigated. A radioisotope method using
[14C]5-hydroxytryptamine as substrate was used. The highest MAO activity was
found in liver followed by brain and kidney (Vmax: 137, 64, and 26 nmol/mg
protein X h, respectively). The Km values did not differ significantly for the
three tissues (liver: 107 mumol/l; brain: 96 mumol/l; kidney: 86 mumol/l). The
MAO activity in liver, brain and kidney was noncompetitively inhibited by all
1-aminoadamantanes studied, each derivative, respectively, showing in all three
tissues about the same percentage inhibition. The inhibitory activity was found
to be increased with the degree of C-alkylation: D-1 (Ki approximately 1 mmol/l)
less than D-145 (Ki approximately 0.1 mmol/l) less than D-191 (Ki approximately
0.07 mmol/l) less than D 178 (Ki approximately 0.02 mmol/l).

PMID: 6891223 [PubMed - indexed for MEDLINE]

[caya]

Thought I would do a med check-in too. I take 4mg 3Xdaily of Requip; 1200mg of "wafer-type" CoQ10, 1500 mg Curcumin and my little teaspoon of DM at bedtime. So far, so good since adding the DM. As I said in previous post, a bad mucus problem in my throat has cut way back and my internal tremors are ten times better since adding the DM March 4th.

Caya

[stevem53]

It is possible that you are sensative or maybe alergic to DM..A half teaspoon is a very small amount, but it seems to go an awful long way

On a lighter note..That stuff has been useless for any cough Ive ever had in my lifetime..:D

[stevem53]

Never thought you'd hear that, did you?:D

but to get serious, Steve is a good example of a standard medication program and that could be why he is doing so well - i.e. no "stealth" MAO inhibitors.

Ann is a tougher guess, but one possibility is the "slow metabolizer" explanation that I mentioned in an earlier post. I forget the exact number but I think five percent of us have a system where a little DM goes a very long way.

So, if those guesses are right, then it would be sensible for someone who didn't want to tackle the "alternative" route to simply do like Steve.

And if someone has a body that doesn't get along with the DM might want to investigate things like green tea extract which offers some of the same protections/

I think there are several lessons here but the big one is that there really can be something important lying right under our noses for years. It is almost a textbook example and I find it encouraging. I nominate Steve for the Big Cheese prize to be shared with Robert, Ashley, Cara, Ann, etc etc :)


Of course Im a good example..People say it all the time..:confused: :D

[BEMM]

The effect of almost two weeks of Robitussin has been a little uneven. I switched to taking it at night, since that sounds like the best time. I still take only 1/4 tsp. Some days I feel markedly better, but not with any real consistency. The DM seems to help my balance, and it helps me stand up from sitting. I still have to struggle to get up, but my "speed" and success rate have increased. Balance and standing up have been two of my worst symptoms, so DM is taylor made for me.
I still take a minimal amount of meds. after 10 plus years of PD. 8 1/2 mg Requip, 1 1/2 pill of 25/100 carb/lev/ 100 mg Amantadine and 1500 mg Curcumine is my daily portion, divided into three dosis.
I have never had 'offs', and on good days I sometimes forget to take my mid day pills until late in the afternoon. Like Steve I am not adversely affected by anything I eat. I have had no ill effects from the DM. My blood pressure is normal to low, and I have not felt any increase in heart rate after taking DM. I will continue taking it. My good days by far outnumber the not so good days, and DM makes them better still.
A little dab'll do ya.......

birte

[ashleyk]

I have been following members comments here on their new experiences with dextromethorphan with a lot of interest and some surprise. My intent on bringing attention to DM was to make people aware that through my own experience with LDN and more importantly the research done on DM and naloxone (naltrexone) at the NIH that there may be a cheap and safe drug, DM, that could slow or stop disease progression. The NIH research on DM claims that it could work in small doses for many brain diseases caused by neuroinflammation such as PD, MS, Alzheimers etc. Since their work was with rodents, I guess they did not get much feedback on symptom improvement but they did seem to see a slowdown in disease progression. So I have been surprised by some of the observations made here on almost immediate symptom improvement for such a small amount of DM and don't know what to make of it. I think the main purpose of DM and LDN is to stop or slow disease progression. I don't know if any of us can claim or know if this new opioid receptor antagonist drug therapy is working for many years to come. It takes a certain amount of courage or foolishness to go down this unbeaten path, especially against your doctors orders.
Ashley

[BEMM]

Part of my feeling of improvement, possibly all of it, might well be placebo effect. I know about myself that I am so very hopeful and optimistic that a new and promising remedy will be efficacious for a while. I took vitamin B- 2 and stopped eating red meat, and for a year and a half, my balance was almost restored. When the effect wore off, I could not be sure if B-2 had stopped working for me, or I had stopped believing that it helped.
Curcumin is still helping after two plus years, so I know that it is not just wishful thinking. DM will have to be suspect for a while. In the meantime I will enjoy the little improvements, whether real or imagined.

birte

[reverett123]

While the current buzz is about neuroprotection, there was quite a bit of work in the 90s addressing neurofunction. It hasn't been followed up but it did show flames beneath the smoke:

1: Mov Disord. 1998 May;13(3):414-7.

A trial of dextromethorphan in parkinsonian patients with motor response
complications.

Verhagen Metman L, Blanchet PJ, van den Munckhof P, Del Dotto P, Natte R, Chase
TN.

Experimental Therapeutics Branch, National Institute of Neurological Diseases
and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA.

The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated
dyskinesias and motor fluctuations were studied in patients with advanced
Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients
reported a beneficial effect at their individually determined optimal DM dose
(range, 60-120 mg/day). The 12 remaining patients either experienced reversible
side effects, particularly mild drowsiness, or decreased levodopa efficacy, and
were therefore excluded from the study. The six responders entered the
double-blind, placebo-controlled, crossover study with two 2-week arms separated
by 1 week wash-out. On the last day of each arm, motor ratings were performed
every 20 minutes for 8 consecutive hours. In addition, motor complications and
Activities of Daily Living (ADL) were assessed using the Unified Parkinson's
Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved
by 25% according to physician's ratings and by 40% according to UPDRS
interviews, without compromising the anti-Parkinson effect of levodopa. Motor
fluctuations and ADL scores also improved significantly. Although the narrow
therapeutic index of DM limits its clinical usefulness, these findings support
the view that drugs acting to inhibit glutamatergic transmission at the NMDA
receptor can ameliorate levodopa-associated motor complications.

PMID: 9613730 [PubMed - indexed for MEDLINE]

1: Neurology. 1998 Jul;51(1):203-6.

Dextromethorphan improves levodopa-induced dyskinesias in Parkinson's disease.

Verhagen Metman L, Del Dotto P, Natte R, van den Munckhof P, Chase TN.

Experimental Therapeutics Branch, National Institute of Neurological Diseases
and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA.

OBJECTIVE: This study assessed the effects of the N-methyl-D-aspartate (NMDA)
antagonist dextromethorphan (DM) on levodopa-induced dyskinesias in Parkinson's
disease (PD). BACKGROUND: Recent experimental evidence suggests that increased
synaptic efficacy of NMDA receptors expressed on basal ganglia neurons may play
a role in the pathophysiology of levodopa-induced motor response complications.
METHODS: DM was given to six PD patients with motor fluctuations in a
double-blind, placebo-controlled, cross-over study. At the end of each 3-week
study arm, patients received several brief i.v. levodopa infusions while
parkinsonian symptoms and dyskinesias were frequently scored. Levodopa
dose-response curves for antiparkinsonian and dyskinetic effects were then
compared for each study arm. RESULTS: With DM, average and maximum dyskinesia
scores improved by >50%, without compromising the antiparkinsonian response
magnitude or duration of levodopa, although in some subjects the levodopa
threshold dose was slightly higher with DM than with placebo. CONCLUSIONS: These
findings support the view that drugs acting to inhibit glutamatergic
transmission at the NMDA receptors can ameliorate levodopa-associated
dyskinesias.

PMID: 9674803 [PubMed - indexed for MEDLINE]

[stevem53]

I took my last dose of Sinamet at 11 pm last night..I took my dose of DM at 12:30 am..I was able to put my slippers on with no problem whatsoever and with out using my hands..(SITTING DOWN)..this morning..(BEFORE TAKING MORNING MEDS)..This is no great feat with my left foot, but near impossible with my right foot..Im lucky if I can get my toes into the opening of the slipper with my right foot..I havent been able to accomplish this in more than 2 years, and Ive done it twice since beginning DM..So Im thinking that as I suspected, that because DM is a dopamine reuptake inhibitor, that it works in tandem with Sinamet, and causes the Sinamet to work more efficiently

Prior to this experiment I was taking my last dose of Sinamet at 7 pm, and taking DM at between 12:30 and 2:00 am, when my last daily dose of Sinamet had no doubt worn off, and had run its course, and usually more nights than not I took the DM at, or closer to 2:00 am

So what Im going to try tonight is using Mirapex as a filler inbetween my afternoon Sinamet and an 11 pm dose because I was feeling kinda funky with a 9 hour span inbetween Sinamet doses

I feel absolutely great this morning!..:)

[stevem53]

It has been one week since I began taking my last dose of Sinamet late at night up to 2 1/2 hours or less before taking my daily dose of DM, and it seems that I feel much better the following day if my last daily dose of Sinamet is still active when I take the DM

My daily drug regimens..(I am and have been undermedicated throughout my dx with pd)

My previous med regimen:..

9:00am - 1 Sinamet 25/100...1 Mirapex .25

2:00pm.- 1 Sinamet 25/100...1 Mirapex .25

7:00pm - 1 Sinamet 25/100

1:00am - 1/2 teaspoon DM

__________________________________________________ ______

My new med regimen:..

9:00am - 1 Sinamet 25/100...1 Mirapex .25

2:00pm.- 1 Sinamet 25/100...1 Mirapex .25

7:00pm - 1 Mirapex .25

11:00pm..(or up to 1/2 hour prior to taking DM)..1 Sinamet 25/100

1:00am - 1/2 teaspoon DM

(I use the Mirapex .25 at 7:00pm dose as a filler dose instead of the usual Sinamet)

Ive had a few friends comment on my improved condition, and a couple have asked me if I was on a new medication..My friend Jim who I have fished with since 1978 goes to Florida every winter..He saw me before he left in December..and he just came back and stopped over this morning..He said that he noticed that I wasnt dragging my foot like I was before..that I only stuttered a little bit..that I was more alert, and looked better than I did in December when he left for Fla

It has been about 5 weeks since I began taking DM daily, and there is absolutely no doubt in my mind that it has improved my symptoms drastically..even my memory has improved

[reverett123]

but keep an eye on the blood pressure, especially if you use requip. Medline has zero hits on the pair but both requip and DM work through the CYP450 enzymes and mirapex does not. I suspect that that was my real problem. BP was around 200/120 after four days and is just now back down.

But those first days were really good. There is something there, just be prudent.

[stevem53]

Thanks for the info Rick..I cant and wont take Requip because it makes me sick..I havent checked my blood pressure yet, and when I do and it happens to be high, the Mirapex is history..actually at this point I dont even really need it anyway..Ill just substitute the 7:00 PM dose with a half tablet of Sinamet

[olsen]

sounds a rather novel use for dextromethorphan--I read about this combo (quinidine and dextromethorphan)being used in Phase 3 trials for ALS patients on another forum--also used for neuropathic pain:

Dextromethorphan-Quinidine Combination Reduces Inappropriate Emotional Episodes in MS





April 18, 2005 (Miami Beach) — A dextromethorphan-quinidine cocktail (Neurodex) effectively addresses the inappropriate laughing and crying episodes experienced by some patients with multiple sclerosis (MS), according to investigators who presented their findings here at the 57th annual meeting of the American Academy of Neurology.

The incongruous laughing and crying episodes, also called "emotional incontinence," are due to pseudobulbar affect (PBA). Dextromethorphan, the active ingredient in most over-the-counter cough suppressant syrups, also binds to the sigma-1 and N-methyl-D-aspartate neuroreceptors and therefore had the potential to address PBA.

"If we gave patients a sufficient dose of dextromethorphan alone to penetrate the central nervous system, the trade-off would be nausea and vomiting," principal investigator Hillel Panitch, MD, said during a press briefing. "However, because quinidine prevents systemic metabolism of dextromethorphan, we can use less dextromethorphan that is yet sufficient to address PBA." Dr. Panitch is a professor of neurology at the University of Vermont College of Medicine in Burlington, where he is the director of the Multiple Sclerosis Center at Fletcher Allen Health Care.

The investigative formulation, also known as AVP-923, consists of 30 mg each of dextromethorphan and quinidine sulfate. In a double-blind, placebo-controlled study, the investigators recruited 150 patients with MS at 22 community and university-based centers to be treated either with the study drug or placebo every 12 hours for 12 weeks. The patients completed a diary and recorded the number of episodes of inappropriate laughing, crying, or both that occurred each day and indicated the medications they took, the times they took them, and any adverse events. The patients had scored at least 13 on a validated self-assessment tool used to evaluate PBA.

The investigators saw the patients in follow-up clinic visits on days 15, 29, 57, and 85. At those times, they obtained patients' clinical chemistry, vital signs, physical examinations, and electrocardiograms. The investigators compared the change in self-assessment score between the treated and placebo patients and also assessed individual change from baseline to the date of each study visit. They also compared the number of laughing and crying episodes and used separate visual analog scale scores for overall quality of life, quality of relationships, and pain intensity.

Treated patients had a clinically and statistically greater reduction in their self-assessment scores than did those who received the placebo (P < .0001). Treated patients also had fewer laughing and crying episodes (P = .0002), a higher quality of life and relationships (P < .0001 and P = .0001, respectively), and less pain (P = .027).

When the investigators evaluated response rates, they found that 84% of treated subjects responded to treatment compared with 49% of placebo patients (P < .0010). The number of emotionally inappropriate episodes per week was 46% lower in the treated group than in the placebo group, with treatment effects observed the first week of treatment.

The rate and severity of adverse events were similar in the two groups, although more patients in the treated group reported dizziness (P = .01). Eleven treated patients (14%) discontinued treatment due to adverse events, as did eight placebo patients (11%). The investigators documented no clinically significant changes in other safety measures.

"I treat many patients with MS and it's refreshing to see a new treatment strategy that appears to have a low rate of side effects," said Michael E. Batipps, MD, who commented on the presentationin an interview seeking outside comment. "We've seen many drugs developed for MS that eventually have been found to have substantial side effects. PBA is a concerning development that we would like to prevent from happening, and the potential to treat it is encouraging. However, although the dextromethorphan-quinidine combination appears to show promise in a subset of MS patients, we will need to see whether these results are confirmed in further studies." Dr. Batipps is a neurologist in private practice in Washington, D.C., with a focus in MS.

The study was funded by Vainer Pharmaceuticals, the maker of Neurodex.

AAN 57th Annual Meeting: Abstract S46.001. Presented April 14, 2005.

Reviewed by Gary D. Vogin, MD

[steffi 001]

....riight...hit me with it. Which cough medicines contain this elixir/Have been like a whirling dervish,obsessed with cough medicines.Am reading all the labels. My kids don`t get chance to take any medicine cos I`ve whipped it from their hot little hands,eager to read the label before they`ve even had chance to get the top off ...and have still not hit on the ingredient yet.

Are certain ones more effective than others.Forgive me if someones listed them somewhere in this thread.No time to wade through it all.just want the stuff. eek. Can it be bought in another form?

gagging...

[rd42]

From page 9 I think, a post from RLSmi:

I think the most important thing to look for in the DM-containing cough preparation is that it contain no additional active ingredient such as guafinesin or polistirex. Also, try to get a pediatric preparation with no more than 7.5 mg / 5 ml (5 ml is one tsp). This makes the small dose of 4-8 mg easier to measure. I prefer the "Simply Cough" which contains 5 mg / ml, but have not been able to find it recently.

The polystirex causes the DM to be slowly released over a period of several hours, and it is apparently important that the small dose "hit" the brain all at once in that critical time a couple of hours before the nightime sleep period when your body normally produces your natural endorphins. Polystirex will prevent this.

Guafinesin is a decongestant, but at the small amount taken probably has little or no effect.

[BEMM]

I am now convinced - 1/2 tsp Robitussin (adult) at bedtime helps me turn over in bed with a little more ease, and helps me sleep longer. I THINK it is still helping my balance. I hate the taste of it.

birte

[EnglishCountryDancer]

In the U.K look for one that says for dry coughs.There are quite a few that follow the above criteria but theyare kept behind the counter so you have to ask for them.My pharmacist friend suggest one asks their doctor for a presciption as it is for off licence use here and chemist would have to refuse to sell it to you if they thought you were purchasing too much.The amount required would hardly alarm any chemist I would have thought.I have had no trouble obtaining it. Besides there are more than one chemist in most towns.

[ashleyk]

This is one of the latest research papers from the NIH on a more potent form of dextromethorphan, 3-HM, shown to be 90% neuroprotective in rodents. In the paper, there is a graph comparing five forms of DM. While 3-HM was 90% effective, the next most effective form seems to be DM at about 70% to 80%. Don't know if 3-HM is sold as a drug.

Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Science/National Institutes of Health, Research Triangle Park, North Carolina, USA.

We investigated the neuroprotective property of analogs of dextromethorphan (DM) in lipopolysaccharide (LPS) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models to identify neuroprotective drugs for Parkinson's disease (PD). In vivo studies showed that daily injections with DM analogs protected dopamine (DA) neurons in substantia nigra pars compacta and restored DA levels in striatum using two different models for PD. Of the five analogs studied, 3-hydroxymorphinan (3-HM), a metabolite of DM, was the most potent, and restored DA neuronal loss and DA depletion up to 90% of the controls. Behavioral studies showed an excellent correlation between potency for preventing toxin-induced decrease in motor activities and neuroprotective effects among the DM analogs studied, of which 3-HM was the most potent in attenuating behavioral damage. In vitro studies revealed two glia-dependent mechanisms for the neuroprotection by 3-HM. First, astroglia mediated the 3-HM-induced neurotrophic effect by increasing the gene expression of neurotrophic factors, which was associated with the increased acetylation of histone H3. Second, microglia participated in 3-HM-mediated neuroprotection by reducing MPTP-elicited reactive microgliosis as evidenced by the decreased production of reactive oxygen species. In summary, we show the potent neuroprotection by 3-HM in LPS and MPTP PD models investigated. With its high efficacy and low toxicity, 3-HM may be a novel therapy for PD.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=17142799&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=15790998&dopt=Abstract

Also, Dr. John Hong, Head of Neuropharamacology at the NIH, will be a speaker at the 3rd annual LDN Conference this October in Tenn. He will speak on opioid receptor antagonists like DM and naltrexone being neuroprotective for PD and Alzheimers. Hopefully, he will be able to suggest the most optimal DM dosage for people even though they don't test with humans, I don't think.
http://www.lowdosenaltrexone.org/events.htm

Ashley

[RLSmi]

3-HM, a major metabolite of DM, is rapidly produced from DM by one or more of a family of drug-metabolizing P450 enzymes in the liver. These enzymes add hydroxy groups to a variety of drugs and other molecules which allows them to be more rapidly excreted, usually in the urine.

The upside of this is that one does not have to separately obtain the apparently more effective neuroprotective 3-HM if one is taking DM.

At least one limitation to this situation could exist if the 3-HM made in the liver and released into the circulation were less able to cross the blood-brain barrier than the parent DM.

[reverett123]

Be alert to possible reactions between DM and other drugs which also use the CYP450 metabolic paths. That may have been my problem since Requip is such. Sinemet is not and I think at least one of the other agonists is not. If you have doubts Google "CYP450" and your drug at a minimum. Then just be extra observant the first few days.

[stevem53]

Today..Its almost 11 pm, and I havent taken any meds since 2 pm this afternoon without any consequences whatsoever..I will be taking my last dose of Sinamet in a half hour..then DM and hour later

Neuro appoimtment on the 11th..Should be interesting

[stevem53]

I saw my neuro yesterday..My motor skill exam was a bit above average, and my BP was 128/80..Down from 140/92 last time..I didnt tell him about the DM

He said to stay the course

[EnglishCountryDancer]

My husband(PWP) who has been diagnosed just over two years, has been taking the appropriate cough medicine for about a month.I am sure I am not imagining it but he seems to be tremoring less often and is walking better although his gait was never that bad.He thinks this is true also .But to him the main advantage has been much better sleep:no more waking at 3am and then being drowsy in the day. The only prescibed medicine he is on is Requip (4mg,4mg 4mg,1mg)Unfortunately, there are too many variable to say it is definately only the DM as he also takes cucumin,cod liver oil. an antioxidant pill and ALC/ALA.The last having been added since starting the cough medicine.
Combination could interact.He takes his blood pressure very reqularly.The reason I have written this follow up is that as he is not on Sinemet it cannot be an interaction with that.Incidently,last time we saw the neurologist he said he thought it would not benifit him or improve his tremor if he upped his Requip so if it works in the same way.....?

[EnglishCountryDancer]

ALA/ALC improves my memory.I am positive about that.

[stevem53]

My husband(PWP) who has been diagnosed just over two years, has been taking the appropriate cough medicine for about a month.I am sure I am not imagining it but he seems to be tremoring less often and is walking better although his gait was never that bad.He thinks this is true also .But to him the main advantage has been much better sleep:no more waking at 3am and then being drowsy in the day. The only prescibed medicine he is on is Requip (4mg,4mg 4mg,1mg)Unfortunately, there are too many variable to say it is definately only the DM as he also takes cucumin,cod liver oil. an antioxidant pill and ALC/ALA.The last having been added since starting the cough medicine.
Combination could interact.He takes his blood pressure very reqularly.The reason I have written this follow up is that as he is not on Sinemet it cannot be an interaction with that.Incidently,last time we saw the neurologist he said he thought it would not benifit him or improve his tremor if he upped his Requip so if it works in the same way.....?

Whatever is responsible for his improvement..Congrats!..Ive been a bit more syptomatic over the past 10 days or so..But still better than I was before..My gait has improved remarkably, but my hands are somewhat symptomatic lately..especially my right hand, which is on my affected side..This is nothing new actually as far as the right hand is concerened..It has taken the hardest hit from my pd, and as a matter of fact I remember vividly the day I began having problems with it..The symptoms didnt develop gradually in it..(arm/hand)..It was ok in the morning..and disabled in the afternoon..It led me to think maybe it was a pulled muscle..but it never recovered from that state

Fatigue?:..Still shows a bit of improvement as well as reduced stuttering

[ashleyk]

This study shows how activated microglial (killer cells), which are believed to destroy dopamine neurons, can be be greatly attenuated by dextromethorphan and another even more effective drug. Though the research was done for drug abuse, it implies that DXM could be used for PD. I don't know what an equivalent human DXM dose would be but this study seems to back Dr. Hongs research done at the NIH.
Ashley

http://www.nida.nih.gov/NIDA_notes/NNvol20N6/Evokes.html
Drs. Kuhn and Thomas injected mice with either MK-801 or DXM and then methamphetamine (5 mg/kg of body weight) 15 minutes later, repeating this sequence four times at 2-hour intervals. A control group of mice received the same regimen, but with saline substituted for methamphetamine. Forty-eight hours after the last injection, the researchers assayed the brains of the mice for Cox-2 and TNF-α, the indicators of microglia activation, and for striatal dopamine levels, a widely used index of damage to dopamine neurons. Dr. Kuhn says, "We found that both DXM and MK-801 significantly reduced the markers of striatal microglial activation associated with methamphetamine exposure and protected against dopamine nerve terminal damage in the striatum. The close association between the ability of MK-801 and DXM to significantly lower both microglial activation and neuronal damage suggests a causal link between the two. It looks as though the damage associated with methamphetamine abuse is the result of microglial action."

[steffi 001]

Since taking this stuff I have only had one bout of dystonia...and that wass on the day I ran out. I normally have excrutiating pain with dystonia for at least nhalf an hour every morning,about 10 minutes after waking...and late at night...and that lasts about the same. To be free of just one symptom os great by me.
Hugs and kisses galore to the person who lightbulbed this .thank you
:hug: xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxx

[EnglishCountryDancer]

So glad to hear that news

[Kathie]

Very interesting discussion about dextromethorphan. My husband has been taking 4.5 mg of LDN (low dose naltrexone) for his PD for a couple years now (along with a couple 25/100 car/lev, 5 mg selegeline, and various supplements). We are wondering if there could be further beneficial effect from taking the dextromethorphan while taking the LDN or is it one or the other, but not both, because they have possibly similar modes of action?? Anyone have any thoughts?

[RLSmi]

in my opinion, Kathie. The published work on DM and suppression of inflammation in animal studies shows that dextromethorphan and naltrexone have the same effect at the same, very low, concentrations. Using both at the same time could result in a total concentration of the two that would be less effective than either one alone.
There is apparently something very unusual about the way this class of drugs produce this anti-inflammatory effect, and keeping the total dose in that 4.5 to 7.5 mg range may be critical to whatever efficacy they may have, i.e., more may not be better.

Robert

[ashleyk]

I have read a lot on LDN and dextromethorphan being used to slow progression of neurological diseases. Not that I understand it all but there seems to be a difference of opinion between the Dr. Bihari people and the NIH group on how these opioid antagonists work. The NIH group seems to believe these drugs work by suppressing neuroinflammation caused by over activated microglial (killer) cells which destroy dopamine producing neurons. In any event, they all seem to believe that these drugs work at very low doses. The research doctor in the email below says not to exceed 10mg a day on naltrexone. If we assume DM and LDN dosages are equivalent, to combine LDN and DM at a combined dose below 10mg may not be risky but no one knows. From what I've seen here, DM seems to have the added benefit of reducing PD symptoms by boosting dopamine production. Maybe LDN has the same effect but there are so few taking LDN for PD, I've never seen that mentioned as a plus.
It seems the drug companies are doing a lot of research on very expensive new drug thearpies that we may or may not see anytime soon. It's a shame that they don't pick up on old established drugs like DM and naltrexone and look at the the work that has come out of Dr. Hong's group at the NIH.
Ashley

Below is an email exchange with one of the developers of LDN. I don't know if it's appropriate to name him, so I guess I shouldn't:
Jan 06
If I could ask you, do you accept the basic claims of Dr. Bihari on the method of action and (probable) effectiveness of LDN?
Response: Low dose naltrexone may have a variety of actions. One certainly is that it works through the Opioid Growth Factor (OGF)- OGF receptor (OGFr) axis. OGF is an inhibitory growth peptide that appears to stablize cells/tissues. This can occur in tissue culture (cells are grown outside the body) and in animals/humans. When we discovered all of this about 25 years ago, the basis for the action naltrexone at low doses is that it acts for 6-8 hours. During this time the naltrexone does not allow the enkephalins/endorphins (opioids) of the body to interact with the opioid receptors on cells/tissues. The cells/tissues compensate for the deprivation of natural endorphins/enkephalins by making more of these opioids, and also making more opioid receptors. Now the trick - if you only block with naltrexone for 6-8 hours, for the remaining 18 hours or so you have high levels of opioids interacting with the opioid receptors and you get a supersensitive reaction. OGF is probably the best example of how naltrexone does its thing. OGF can repress cells, but most probably has effects on the immune system under in vivo (entire animal/human) situations. Would you recommend LDN to a friend if they had a disease in which LDN could stop progression?
Response: The only legitimate study that I have (we are talking about statistics, etc) for low dose naltrexone is one that I know about - this is concerning Crohn's disease. And even this is a preliminary report. The internet is filled with claims about LDN - including some from doctors. Please be aware that science is not serving as underpinnings for these claims.
Now, in saying this, please let me say that LDN has many potentially terrific effects. But all of this should be done under a physician's supervision. Take the LDN once a day - in our patent on this we recommended dosages of 3-10 mg of naltrexone/daily. I believe many now are using 4.5 mg/day - that is fine and was derived from our claims. Do not take this more than once a day. Do not take this if you are using opioid-based pain medications. Have a doctor examine the patient prior to beginning medication, making special assessment of the signs/symptoms that you want to treat. Have a follow-up visit in one month, and again in the 2nd month. Compare the outcomes to the original data. If nothing changes - or things decline - try a new medication.
I've viewed your many publications (not that I can really understand them) and noticed that most of your work now is in Opioid Growth Factor. Is that in any way related to how LDN works? Have you given up on naltrexone (LDN) as a disease treatment?
Response: Our discovery of LDN (we call it intermittent opioid receptor blockade) was made in a serendipity fashion, while looking for agents to alter growth (e.g., cancer, development). In actuality, LDN is really not doing anything to growth/biological activity. It is really interrupting the body with its natural chemicals - the enkephalins/endorphins. Therefore, our mission has to identify the precise opioid in the body that influences biological activities - this is methionine enkephalin - what is called opioid growth factor (OGF) to distinguish it from methionine enkephalin's role as a neurotransmitter in the nervous sytem. We then went on to identify the receptor for OGF - this is now called the OGF receptor (OGFr). We then went on to clone and sequence the gene for OGFr - it is one of the 20,000 genes in humans, and we know its chromosomal location. In fact, OGF is now being used in phase II clinical trials (we already passed phase I and have a publication in a journal on this) by our group to treat pancreatic cancer. How the OGF-OGFr axis does its thing - the mechanisms - as well as using this now to help patients, really is our focus.

[ol'cs]

... but is nevertheless very useful.
Please read this
http://www.continuingeducation.com/pharmtech/dextromethorphan/dextro.pdf

I know it's a bit tough for non-scientists, but I think that it's so well written and up to date that just about anybody can gather the pertinent points as it relates to the pharmacology of DM (Dextromethorphan)

Now for my interpretation and comments. DM is a strange duck in it's pharmacology. It is said not to be an opiod mu agonist (narcotic, dependancy, increasingly tolerant so one tends to up the dose to get the same effects); but it either is a low affinity mu, kappa, delta or sigma ligand (the subsets of opioid receptors, that have different modes of action as opioids) because it DOES act like an opioid agonist in many respects. The bodies ability to metabolically "racemize" DM and produce the known opioid mu agonist "Levorphan" (simply, the mirror image of DM, but with totally diffferent action in the body; a narcotic with all the "bugs" associated with a strong narcotic) must be considered in it's overall effects in humans.
What I find interesting and possibly at the heart of what we are observing is that DM is an antagonist to the "Excitatory amino acids" specifically NMDA. When the brain is flooded with excitatory amino acid neurotransmitter release, that is likely the cause of dyskinesia. Antagonizing these neurotransmitters quells their effects and so for PWP it calms us down releasing us from the muscular contractions that are associated with dystonia and dyskinesia. Another good thing is that is develops tolerance apparently very slowly, if at all.
Please take the time to read this article, even if you get bored at times , you will perk up at certain paragraphs.
DM has long been known to cause some pretty spacey trips in the 1000-1300mg range (i mean like a powerful hallucinogen, and by no means "fun" at all).
That it has weak serotonergic reuptake inhibitatory properties shouldn't be a mystery, it appears that DM "hits" a lot of neurotransmitter systems in various ways. Last, since naltrexone is a pure opioid antagonist, I would think that you would simply cancel out the effects of both drugs:eek: , cs

[reverett123]

How are those of you testing this one doing now?

[stevem53]

How are those of you testing this one doing now?

As far as symptomatic relief, I have become so physically busy with fishing, yard work, and daily chores etc, that it has become impossible to measure syptomatic relief..The good news is that I have been able to what I have set out to do

As far as neuro protection/progression..Its still too early to tell

[steffi 001]

I personally can can honestly say that my dystonia was somewhat reduced whilst on Dextra thingy ..sorry..can` t write it all.I was taking it in Covonia cough medicine...and decided to stop whilst taking Metatone.The dystonia returned but not as aggressively.I am still just on Metatone,wondering whether I could take both this and the Covonia at the same time.I should,at my last neuro apptment be increasing my ropinarole but decided not to.Instead I am looking to drop one of my daily tablets..not complete doses.I take 8 a day so will start by dropping one for a week or so,then be brave and drop another.
Dextra...doo da...DEFINATELY suppressed the dystonia.
My energy level is fantastic which I put down to the Metatone.
Would appreciate advice as to if I can take them both
Oh...I am also detoxing at the minute.

Sorry./..can` t wade through the lengthy scientific posts so could some brainy person just say YES or NO. I will be happy with "simple"
Suits me to a T
Thank you for bringing this knowledge to light.It has been great to be free of the agony of a twisted foot and lower leg for a while.
I can stand a great deal of pain but dystonia is something else.

x

[steffi 001]

I asked my GP if I could obtain Dextra.....in a tablet form,hence doing away with the alcohol content.It doesn`t affect me but I know some folk here are intolerant of alcohol in formula`s.I was surprised at his answer...that it is not on the UK drug registry and he thought could be addictive.I haven`t found the cough medicine addictive..but would be interested as to how you guys take it/..Again sorry...can`t go wading through the posts....too much else to do :)

[KC Tower]

I asked my GP if I could obtain Dextra.....in a tablet form,hence doing away with the alcohol content.It doesn`t affect me but I know some folk here are intolerant of alcohol in formula`s.I was surprised at his answer...that it is not on the UK drug registry and he thought could be addictive.I haven`t found the cough medicine addictive..but would be interested as to how you guys take it/..Again sorry...can`t go wading through the posts....too much else to do :)

Why wouldn't one simply buy a cough medicine containing DM and no alcohol??

Ken

[steffi 001]

..good point...can you reccomend one?
x

[KC Tower]

I asked my GP if I could obtain Dextra.....in a tablet form,hence doing away with the alcohol content.It doesn`t affect me but I know some folk here are intolerant of alcohol in formula`s.I was surprised at his answer...that it is not on the UK drug registry and he thought could be addictive.I haven`t found the cough medicine addictive..but would be interested as to how you guys take it/..Again sorry...can`t go wading through the posts....too much else to do


Why wouldn't one simply buy a cough medicine containing DM and no alcohol??

Ken

..good point...can you reccomend one?
x


Looking in the pharmacy or whatever it is called over there would be a good place to start for most.

Buckleys DM (sucrose free alcohol free) is one sold in Canada.

[ashleyk]

In post #126 by ol'cs, he provided a PDF file on Dextromethorphan FYI for Pharmacists. At the end of the report, page 17, there is a table of various DX products with their strengths and ingredients. Also, my earlier thought that LDN (naltrexone) and DM could be combined is probably wrong. On page 5, it is stated that naloxone (naltrexone) is an antidote for DM overdose.
http://www.continuingeducation.com/p...han/dextro.pdf (http://www.continuingeducation.com/pharmtech/dextromethorphan/dextro.pdf)

Also, in the lowdosenaltrexone web site under "Latest News - May" the researcher below treated 10 people with various immune disorders, MS, lupus, RA (no PD) with 4.5mg naltrexone. DM is aso an opioid. It's not a long report and is easy to read.
"Niles Bauer, PhD candidate, Department of Microbiology and Immunology, College of Medicine, University of Arizona, supplied a copy of a presentation (http://www.lowdosenaltrexone.org/_mm/Bauer_Presentation_Mar_2007.pdf) to his department in March 2007. He observed “profound” improvements within a month after the start of LDN treatment in people with a wide variety of autoimmune disorders."
http://www.lowdosenaltrexone.org/ldn_latest_news.htm

I'm curious as to how many here are taking DM and what their thoughts on the whole thing are? Ashley

[RLSmi]

:) As i wrote on a recent weekly check-in, I'm taking about 5mg of DM each night (approx 2/3 tsp. of "Pedia Care Cough" with 7.5mg DM per tsp.). I still need my 2 X Sinemet cr 50/200 generic and 1/2 of a regular Sinemet 25/100 generic each day; also take Amantadine and CoQ10. Neuro is delighted with my status.

Dx 2001, started on Sinemet and Amantadine. Decreased Amantadine in 2002 due to swelling feet and ankles. CoQ10 begun 2002, DM begun 2003.

I still work in the yard 4-5 hrs each day (with breaks) and my wife says she sees no symptoms except for the early morning "shuffles" before the meds kick in. Still have occasional "PEE ALERTS", depending on what and how much I drink.

[stevem53]

I am still taking DM too..Ive been out fishing and doing other odds and ends, yard work, getting prepared for fishing the following day, food shopping, etc..Ive been very active lately, moreso than a year ago..Still at 3x25/100 per day with the exception of substituting with a 50/200 in the morning before I go out fishing..I went out 4 days in a row last week, but couldnt go on the 5th day because of fatigue and bad weather

[RLSmi]

to see how many on the forum are now taking low-dose dextromethorphan (DM) or low-dose naltrexone and your impressions of sympptom progression over the last six months. If you prefer, send your reply to me by pm.
Robert

[stevem53]

to see how many on the forum are now taking low-dose dextromethorphan (DM) or low-dose naltrexone and your impressions of sympptom progression over the last six months. If you prefer, send your reply to me by pm.
Robert

I am still taking 5-8 mg daily

I have toe curling problems recently on my right, most affected side..I dont know if its dystonia, or progression..or if dystonia = progression

My left hand has lost some coordination..but my gait has improved..I would say that Im doing ok and that symptoms are playing musical chairs..Fatigue a tad lessened

Except for the toe curling..(on one foot)....Im more or less at status quo

[EnglishCountryDancer]

Husband is still using the cough medicine but also using a number of supplements and working hard at the gym so difficult to sort out what, if any, are having a result.Touch wood, there seems to be no, if not very little progression.Two separate people, without prompting, said he seemed a little better:one was the gym instructor and one a friend of long standing.I do not know:the tremor has not diminished but his face seems a lot,lot more mobile.Still on13 mg Requip only.Time since tremor became so troublesome went to doctor:3.5 years.+

[reverett123]

I will not hijack this thread so if there is any interest we can jump to a new one but the reply from Englicsh conutry dancer got me to thinking about how difficult it is to sort out what we are doing and what is working.

If those of us experimentinting with anything used our signature line like a little billboard like below we could compare. it would be of some value wouldn't it?

[reverett123]

...I am sleepy? I'm not even going to try to edit that one. :D :D :D

[EnglishCountryDancer]

We could see if there was a common thread.We would have to discount the placebo effect.Here goes:
Curcumin
Concentrated Omega 3
True food Natural VitaminE
Acetyl Lcarnitine&alpha lipoic acid marketed as Alpha(It is important to take these together...synergy)
True Food Maxi Q10 Only 120 mg(Only just started this because of expense)
Super antioxidant
Suitable cough medicine .
True food indicates it has been treated to maximise its potential
Amount taken is manufacturers maximum recommended dose except for cough syrup
All this costs a fortune but we think it worth a go. We will not really know if it is worth it for years
PLUS
40 minutes in gym doing running(yes running) cross trainer and now cycling.This is done on about 4 or 5 days a week.On at least one of the days he does not go to the gym he Morris Dances(The bells and hankies and stick variety)

[ashleyk]

It's been just over 36 months since I started taking 4.5 mg of naltrexone, LDN. At that time they said my increasingly worse tremor was MS but 4 months later I started Sinemet which worked and so I now have PD. Since that time Mirapex was added to my PD and Sinemet was reduced somewhat. I still take relatively low amounts of both drugs maybe because I'm still early onset?. I also take 400 mg of Q10 and some magnesium daily. I'm now 58 and my first tremor symptoms began maybe 5 years ago. My tremor is gone for now and outside of the drug side effects and poor sleep and low blood pressure, I manage quite well. I think I can say my PD has not progressed but it's hard to say. I hope it's because of the LDN. I've read a lot on what to expect about PD progression when beginning Sinemet and I am still not clear where I should be along the curve. I still wait for the other shoe to drop on progression but taking LDN gives me some hope for now that maybe I'll be ok. Note: I base most of my believe in LDN on the work done by Dr. Hongs group at the NIH. They have shown that low doses of opioid receptor antagonists like naloxone, naltrexone and dextromethorphan can slow or halt simulated PD in rodents.
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=15791005&dopt=Abstract