Posted by JohnX2 on April 3, 2002, at 14:42:27
In reply to Re: Kramer- Question on Mode of Action - Provigil » IsoM, posted by SLS on April 3, 2002, at 10:54:29
> > Do you know if Cephalon, the parent company of Provigil, is doing any follow-up studies on it trying to determine Provigil's mode of action in the human brain?
>
> Hi.
>
> I haven't been keeping up with it, but the last time I checked, the only property that researchers seemed to be convinced of is that Provigil (modafinil) promoted an increase in extracellular glutamate. Glutamate is by far the most widespread excitatory neurotransmitter in the brain, and it is thought that Provigil increases glutamatergic activity in several key areas responsible for both wakefulness and vigilance/mood. It is my impression that increased wakefullness is promoted by Provigil in the hypothalamus, and increased vigilance and mood elevation in the hippocampus.
>
> According to what I had read, Provigil does not act as a ligand to stimulate directly any NE receptor. It is not a NE alpha-1 agonist.
>
>
> - ScottFellas,
I posted a bunch of links on modafinil studies starting here (just a short while ago in fact):
http://www.dr-bob.org/babble/20020322/msgs/100358.html
The studies implied mechanisms showing direct/indirect increases in serotonin conductance, reductions in Gaba, and increases in glutamate conductance.
Its possible to increase serotonin conductance by agonizing somatodendric alpha-1 noradrenaline receptors on serotonergic neorons, but I ?believe? that antagonist medicines at alpha-1 noradrenaline receptors do not block provigil's action (hence the thought that it does not bind to the sight?).
Regards,
John
poster:JohnX2
thread:101413
URL: http://www.dr-bob.org/babble/20020402/msgs/101701.html