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Re: Provigil-Modafinil-Adrafinil? Rick

Posted by kregpark@yahoo.com on January 6, 2002, at 17:20:34

In reply to Re: Provigil-Modafinil-Adrafinil? kregpark@yahoo.com, posted by Rick on January 6, 2002, at 14:58:37

Hi Rick -

I think you make some good points.

Provigil: I did see the reference to haloperidal on Medline, and the PDR blurb (newer studies seem to contradict some of that). Haloperidal versus clozaril challenge seem contractictory, as well as NE challenges. Some stuff says they don't know *what* is the mode of action, but otherwise what I see implicates DA. Regardless how it works, the effect seems to MIMIC closely actual DA + 5ht enhancement. ie; Treating it that way can be useful.
Klonopin: Not a dopamine agonist. Niether is gabapentin clearly, (often even sedating), but how is it that some who take gabapentin for SP develop mania, and how does gabapentin help prevent bipolar swings to "low dopamine" state?
Serzone: Serzone (similar to the older trazodone) is a basically sedating and/or agitating sertononin BLOCKER. Newer data show very little whole level serotonin increase, insignificant compared to the SSRI's. Dr's used to wonder why it didn't seem to help significant depression.

I've never seen anyone suggest 100% DA drugs for SP. I'm only saying that low dopamine to exist in a substantial number of SP patients.
The higher (factor of 5) incidence of Parkinson's in SP versus non SP folks may provide clues.
Caffeine (mild dopamine and choline enhancement) appears to dose dependently prevent later life onset of Parkinson's, reduction up to factor of 5 in those drinking somethiing like 5 cups of coffee a day.
Smoking (MAOI-B) maybe other, reduces Parkinson's about factor of 5 also.

kregpark


The article - I haven't read but did see abstract and liked it! I remember showing to my Dr. who has few SP patients.

In the only such study I've seen, Nardil increases DA and NE slightly and more robustly.


------------

> Craig -
>
> Most of the studies I've seen suggest that modafinil has minimal dopaminergic activity.
> A quote from the mongraph:
>
> Modafinil is not a direct- or indirect-acting dopamine receptor agonist and is inactive in several in vivo preclinical models capable of detecting enhanced dopaminergic activity. In vitro, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. In a preclinical model, the wakefulness induced by amphetamine, but not modafinil, is antagonized by the dopamine receptor antagonist haloperidol.
>
> Neither have I seen anything to suggest that clonazepam is dopaminergic. In fact, some work at Ontario's McMaster University (which coincidentally is one of the primary Social Phobia research insttutions) has suggested that clonazepam may have antidopaminergic effects in the striatum:
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9517437&dopt=Abstract
>
> Now, as for serotonergic AD's, that's a very different story. One theory of their frequent efficacy in social phobia relates to the dopamine reuptake blockade some of the SSRI's possess. And we know that the MAOI Nardil which is has an excellent track reord treating SP, preserves dopamine in addition to serotonin and noradrenaline.
>
> But the point is that these agents that have shown success treating SP are NOT 100% dopaminergic meds. Again, studies of purely dopaminergic drugs - whether direct or indirect acting -- have all failed to produce significant benefit in social phobia treatment, and have sometimes worsened the condition.
>
> Reiterating, I'm by no means arguing the point that dopamine dysfunction could be a key factor in Social Phobia (as are serotonin, noradrenaline and GABA). And that very likely applies to me, too. I'm only stating that, for whatever reason, purely dopaminergic meds tested thus far generaly don't work, and may in fact increase anxiety. In essence, the "brute force" methods for preserving/increasing dopamine don't seem to work for SP. But that doesn't mean dopamine enhancement couldn't be very beneficial to SP in a less direct, synergistic way. Note that Wellbutrin, which has proven helpful in at least some cases of SP, has adrenergic activity in addition to its dopaminergic properties.
>
> BTW, 2.5 mg selegiline diminished the effectiveness of my Klonopin a bit, but provided enough cognitive, energy, and sexual benefits that I'd likely try adding it back if I had to give up Provigil -- assuming, for safety's sake, that I was still off Serzone.
>
> Rick
>
> P.S. If you haven't already done so, I suggest you get your hands on the fascinating article "Drugs in Development for Social Anxiety" Disorder: More to Social Anxiety Than Meets the SSRI. The 11- page (not including references) article was written by Van Ameringen et, al. of McMaster, and is in the October 2000 issue of "Expert Opinion in Investigational Drugs."


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