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Re: Provigil Dop Re-Upt Inhibitor, PDR Book.

Posted by JohnL on September 22, 2000, at 4:02:36

In reply to Provigil NOT Dopamine Re-Upt Inhibitor, posted by Darby on September 21, 2000, at 22:19:09

> I must disagree with the description of modafinil (Provigil) as a dopamine reuptake inhibitor. The only information I'm aware of that it has any dopaminergic action at all relates to very limited secondary actions on dopamine in the nucleus accumbens of the brain. Modafinil seems to be primarily a noradrenergic-acting compound with some GABA reducing actions. Its dopaminergic actions seem to be very limited.
>
> Thanks,
>
> Darby

Darby,
I was just basing information on the year 2000 Physician's Desk Reference Book, since it's the most commonly used source of information for doctors and psychiatrists with the latest scientific evidence. To date Provigil has shown no binding affinity to any of the common receptor sites, including NE, serotonin, GABA, histimine, and others. But it does bind to the dopamine receptor causing an increase of extracellular dopamine levels. Strangely, though it shows no direct NE alpha agonism, its effects can be reversed by alpha1 antagonists. It's rather wordy and lengthy, so I've just summed it up. But that's what it says. Whatever unknown mechanisms Provigil exhibits, one of them that is known is dopamine reuptake, but no increase in dopamine output. I'm sure there must be other mechanisms at play, but at this time they are not clinically known. Whatever noradrenergic or GABA effects Provigil might have, according to the PDR they are either nonexistant or clinically irrevelevant. Maybe you have some information that is more updated and more formal than the PDR book?

What always amazes me is how they invent these medications and yet they don't know what they do. How can they do that? Weird.
John


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