\[quote=Arsippe;959899That's why I'm taken with your account of it inciting tremors that you may not have had otherwise....
Ask lots of questions before trying this class of drug. While Isradapine was deemed safe in clinical trial safe for PWP, it was only tested for effect on blood pressure. However, two older calcium channel blockers that are in the same class as Isradapine have actually induced Parkinsonism. In most cases, PD like symptoms went away once drug is stopped, but not all were reversible; interestingly, tremor persisted in many people. Results of CCB Induced Parkinsonism studies in the 90's:
Despite a global improvement, cognitive and mood disturbances subsided slowly, and tremor persisted in most patients. After 18 months of CCB withdrawal, 44% of patients had depression, 88% had tremor, and 33% still had criteria for diagnosis of parkinsonism. During the survey, only three patients were found to be fully recovered (3 0f 32). 1992
Most patients with CCBIP improved spontaneously. Twenty-four months after CCB withdrawal, only 14% exhibited akinetic rigid syndrome, but 92% of patients still had tremor. 1998 http://www.ncbi.nlm.nih.gov/pubmed/18591113/
I would be very reluctant to try anything in this class without having some questions answered first. The first question is obvious; how can
drugs in the same class be at odds like this? This theory on calcium influx is interesting, but how can an inhibitor be neuroprotective in some and cause parkinsonism in others? I also think it is far too specific a target specific for a disorder with such a wide variety of causes.
My other question is how does this theory account for loss of norepinephrine? It has been established that we lose more of that neurotransmitter than we do dopamine, so I am highly skeptical of any study that only looks at treating loss of dopamine. Also, there is far more evidence that alpha-syn plays a main part in PD, so how does the calcium theory leave any room for protein misfolding?
Looking at Lab Rat's experience in light of the tremor readings in the above studies is enough to scare me off and the holes in the theory just substantiate it. I am probably wrong to be so skeptical but that association with PD is scary. I don't meant to upset anyone who has benefit from it , and maybe I know squat and drugs in this class are like apples and oranges. If they would simply explain that I would feel much more at ease, but I have yet to see it.
Lastly, alluding to LFAC's costly four year experiment, there is very little evidence it is even effective in humans. According to MJFF, Phase II trial established that doses up to 10 mg (20 mg was max) were deemed the max tolerable for PWP, yet there was not a hint of efficacy. If the efficacy tipping point is 12 mg then what? I would be very surprised if this sees Phase III. Trial researchers admitted the following on Phase II results. If the drug showed no real efficacy at 10 mg vs. placebo what is the point of going forward?
And by and large, there was little to no efficacy signal shown, although we believe that there was a hint of difference between the active drug and placebo, and in a positive way.
I agree with LFAC, given full-disclosure this seems a dead end so I wonder too...why all the hype?!?