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Ldopa to dopamine to epinephrine?

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Unread 07-28-2008, 10:43 AM   #1
reverett123
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Default Ldopa to dopamine to epinephrine?

This morning I got started a little slowly but otherwise was on track. Headed for the shower with things on my mind but not overly stressed. Noticed a shift toward "off" and by the time I was through was, indeed, off. Took second round of meds and settled in to wait.

While waiting a crow let loose a single "Caw!" outside and it went like a lightning bolt through me (i.e. the startle reflex). And that set me to thinking

Ldopa is converted to dopamine and dopamine is converted to epinephrine/adrenaline. But what is the mechanism that controls this and does it function properly in PD? Among other things that come to mind-

Does epinephrine ("E") take priority over dopamine ("DA")?. I would assume so since E is critical to the fight or flight response. And if our ForF is on more than normal, does that account for part of our low supply of DA?

Conversely, if the controls are set wrong and produce more E than needed, would that account for the increased ForF? Or is it, as I suspect, an interaction of both with each feeding the other?

How does flooding our system with Ldopa affect things? Is it a passive reservoir that our body draws from as needed? Or is it an active factor that stimulates the production of one or both of DA and E?

Just wondering....
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Born in 1953, 1st symptoms and misdiagnosed as essential tremor in 1992. Dx with PD in 2000.
Currently (2011) taking 200/50 Sinemet CR 8 times a day + 10/100 Sinemet 3 times a day. Functional 90% of waking day but fragile. Failure at exercise but still trying. Constantly experimenting. Beta blocker and ACE inhibitor at present. Currently (01/2013) taking ldopa/carbadopa 200/50 CR six times a day + 10/100 form 3 times daily. Functional 90% of day. Update 04/2013: L/C 200/50 8x; Beta Blocker; ACE Inhib; Ginger; Turmeric; Creatine; Magnesium; Potassium. Doing well.
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Unread 07-28-2008, 12:54 PM   #2
rosebud
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Default Wellll...

I hope your just thinking out loud, because I'd be surprised if there are answers to that rack of questions. We take levodopa and our body (brain)makes decisions about what its going to do with it. Sending it to the brain is only one option...there are probably more options than we are even aware of at this point in time. I am quite sure my levodopa gets blocked from time to time and ends up in my adrenal system...thus causing me more problems than it cures. Is this the first time you've had this experience?
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Unread 07-28-2008, 02:32 PM   #3
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Default oh lordy no

Regular feature. But it is the first time I had a crow give me a hint about it.

No, I consider the question of stress effects and reactions to be the 600 pound gorilla in the room. Consider-
1- We can convert DA to E
2- Presumably, we do that when stressed
3- We are highly stressed just struggling to maintain a sitting position.
4- There is a finite supply of DA available. How much can be converted to E without triggering symptoms?
5- When symptoms are triggered, stress goes way up.
6- Depletes DA even more and sets up a feedback loop.
7- After a time with PD, just the anticipation of symptoms can increase stress. How much? Enough to start a feedback loop?
Feedback loops are strange creatures. Hold a microphone in front of a speaker hooked to it and the slightest sound sets the loop in motion and blasts away. What is the equivalent in PD? The feeling of a slight increase in stiffness? Is it even necessary that it be conscious?

Is it possible to stop that reaction if it is identified?

Quote:
Originally Posted by rosebud View Post
I hope your just thinking out loud, because I'd be surprised if there are answers to that rack of questions. We take levodopa and our body (brain)makes decisions about what its going to do with it. Sending it to the brain is only one option...there are probably more options than we are even aware of at this point in time. I am quite sure my levodopa gets blocked from time to time and ends up in my adrenal system...thus causing me more problems than it cures. Is this the first time you've had this experience?
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Born in 1953, 1st symptoms and misdiagnosed as essential tremor in 1992. Dx with PD in 2000.
Currently (2011) taking 200/50 Sinemet CR 8 times a day + 10/100 Sinemet 3 times a day. Functional 90% of waking day but fragile. Failure at exercise but still trying. Constantly experimenting. Beta blocker and ACE inhibitor at present. Currently (01/2013) taking ldopa/carbadopa 200/50 CR six times a day + 10/100 form 3 times daily. Functional 90% of day. Update 04/2013: L/C 200/50 8x; Beta Blocker; ACE Inhib; Ginger; Turmeric; Creatine; Magnesium; Potassium. Doing well.
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Unread 07-28-2008, 03:21 PM   #4
RLSmi
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Default

My impression is that epinephrine synthesis occurs primarily, if not exclusively, in the adrenal medulla. Release of epi from there stimulates the F or F response. I don't know if flooding our circulation with Dopa causes excess epi synthesis or release. If i'm not mistaken, much of the epi-stimulated F or F response is mediated by the peripheral parasympathetic nervous system, but I don't know about the central nervous system's role in that response.
The beneficial effects of Dopa therapy in PD depends on the capacity of remaining dopaminergic neurons to absorb the pre-formed Dopa and convert it to DA without needing to first go through the tyrosine hydroxylase step to form Dopa from tyrosine.
I have experienced the "electric shock" sensation many times in response to sudden noise, especially when beginning to fall asleep.
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Unread 07-28-2008, 07:18 PM   #5
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Default No answers

Just 2 experiences:

The "Red" Novacaine at the Dentist has epinephrine in it and it makes me extremely jittery -long before pd! - so i always ask for the "white". I think they prefer the red because it lasts longer, controls bleeding.

There's a relatively new body work/physical therapy that "downregulates" the nervous system. I had a session and found it seemed to do that. I think I would benefit from regular sessions of it. PRRT - Primal Reflex Release Therapy. Google.
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Unread 07-28-2008, 08:53 PM   #6
reverett123
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Default Found this...

Helps a little and flies in the face of what we are told about protein-

Tyrosine, Phenylalanine, and Catecholamine Synthesis and Function in the Brain
http://jn.nutrition.org/cgi/content/full/137/6/1539S

Aromatic amino acids in the brain function as precursors for the monoamine neurotransmitters serotonin (substrate tryptophan) and the catecholamines [dopamine, norepinephrine, epinephrine; substrate tyrosine (Tyr)]. Unlike almost all other neurotransmitter biosynthetic pathways, the rates of synthesis of serotonin and catecholamines in the brain are sensitive to local substrate concentrations, particularly in the ranges normally found in vivo. As a consequence, physiologic factors that influence brain pools of these amino acids, notably diet, influence their rates of conversion to neurotransmitter products, with functional consequences.
*
Elevating brain Tyr concentrations stimulates catecholamine production, an effect exclusive to actively firing neurons. Increasing the amount of protein ingested, acutely (single meal) or chronically (intake over several days), raises brain Tyr concentrations and stimulates catecholamine synthesis.
*


Quote:
Originally Posted by RLSmi View Post
My impression is that epinephrine synthesis occurs primarily, if not exclusively, in the adrenal medulla. Release of epi from there stimulates the F or F response. I don't know if flooding our circulation with Dopa causes excess epi synthesis or release. If i'm not mistaken, much of the epi-stimulated F or F response is mediated by the peripheral parasympathetic nervous system, but I don't know about the central nervous system's role in that response.
The beneficial effects of Dopa therapy in PD depends on the capacity of remaining dopaminergic neurons to absorb the pre-formed Dopa and convert it to DA without needing to first go through the tyrosine hydroxylase step to form Dopa from tyrosine.
I have experienced the "electric shock" sensation many times in response to sudden noise, especially when beginning to fall asleep.
__________________
Born in 1953, 1st symptoms and misdiagnosed as essential tremor in 1992. Dx with PD in 2000.
Currently (2011) taking 200/50 Sinemet CR 8 times a day + 10/100 Sinemet 3 times a day. Functional 90% of waking day but fragile. Failure at exercise but still trying. Constantly experimenting. Beta blocker and ACE inhibitor at present. Currently (01/2013) taking ldopa/carbadopa 200/50 CR six times a day + 10/100 form 3 times daily. Functional 90% of day. Update 04/2013: L/C 200/50 8x; Beta Blocker; ACE Inhib; Ginger; Turmeric; Creatine; Magnesium; Potassium. Doing well.
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Unread 07-30-2008, 07:20 PM   #7
ol'cs
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Default To All....

Eventually we get to the point where we are suffering so badly from one or two or many aspects of PD that we just want to get a hand around PD"S throat and one snap, fixed
All of the questions and replies above are valid. WE need answers to what will at least allow us to tolerate this monster. I could go on and on about what we don't know, but what's the point. For many of us, now grown old with "young PD", enough is enough. At least drug us into feeling not quite like getting out of bed in an Alaskan cabin in the woods with no heat or electricity, alone, and in the dead of winter, and with a broken leg.
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Unread 07-30-2008, 08:20 PM   #8
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Default It's official

We are all complete nerds. How often did you picture yourself winding down in the evening with this conversation by choice?

Helps a little and flies in the face of what we are told about protein-
Tyrosine, Phenylalanine, and Catecholamine Synthesis and Function in the Brain
http://jn.nutrition.org/cgi/content/full/137/6/1539S

But I've also seen Everett dance on You Tube.
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Unread 07-30-2008, 10:39 PM   #9
reverett123
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Boogie for Science!

Quote:
Originally Posted by paula_w View Post
We are all complete nerds. How often did you picture yourself winding down in the evening with this conversation by choice?

Helps a little and flies in the face of what we are told about protein-
Tyrosine, Phenylalanine, and Catecholamine Synthesis and Function in the Brain
http://jn.nutrition.org/cgi/content/full/137/6/1539S

But I've also seen Everett dance on You Tube.
paula
__________________
Born in 1953, 1st symptoms and misdiagnosed as essential tremor in 1992. Dx with PD in 2000.
Currently (2011) taking 200/50 Sinemet CR 8 times a day + 10/100 Sinemet 3 times a day. Functional 90% of waking day but fragile. Failure at exercise but still trying. Constantly experimenting. Beta blocker and ACE inhibitor at present. Currently (01/2013) taking ldopa/carbadopa 200/50 CR six times a day + 10/100 form 3 times daily. Functional 90% of day. Update 04/2013: L/C 200/50 8x; Beta Blocker; ACE Inhib; Ginger; Turmeric; Creatine; Magnesium; Potassium. Doing well.
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Unread 07-31-2008, 03:18 AM   #10
petesmusic
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Hi, I read the link but I am not astute enought o know the implications. I do know that protein inhibits the dopamine in my case so I abstain as much as possible.
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