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Re: More:Provigil poop out;klono counteracts provigil?

Posted by Rick on June 11, 2000, at 16:49:29

In reply to Re: More:Provigil poop out;klono counteracts provigil?, posted by SLS on June 11, 2000, at 10:27:50

(NOTE: Given the posting difficulties I've had recently, this post may end up getting cut-off in the middle. If so, I will post the second half in a follow-up message)

Scott -

You clearly have a deeper knowledge of pharmocology than I do. I found your observations very interesting.

I've never used adrafinil, and have little knowledge about it other than what I've read here on Psycho-Babble and the smart-drug sites. What I do know is that in France, quarterly liver-function tests are now required for adrafinil users because there have been some cases of significant hepatic toxicity. Modafinil (Provigil) does not share this requirement.

From what I've read recently, Provigil's mechanisms are still mostly a mystery. It is still usually referred to as an adrenergic drug, although a recent review from U.S. Pharmicist says that the original theory of direct or indirect NE alpha-1 agonism has fallen out of favor. Nonetheless, it appears that that Provigil won't promote wakefulness unless the alpha-adrenergic system is functioning properly. As for poop-out, again I can't speak to adrafinil, but as was noted earlier in the thread, poop-out reports reflect Provigil's tendency to sometimes start self-inducing production of metabolizing enzymes. The manufacturer says that this be corrected by a modest (and temporary?) dosage increase. I saw one nine-month study that showed sustained effectiveness (at a constant dose) for all responders.

The following from Lexi-Com seems to sum up the current theories pretty well, incuding the possibility of GABA reduction effects at certain sites:

"The exact mechanism of action is unclear, it does not appear to alter the release of dopamine or norepinephrine, it may exert its stimulant effects by decreasing GABA-mediated neurotransmission, although this theory has not yet been fully evaluated; several studies also suggest that an intact central alpha-adrenergic system is required for modafinil's activity; the drug increases high-frequ


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