Posted by SLS on October 29, 2001, at 17:28:48
In reply to Re: modafinil pharmacology » SLS, posted by Elizabeth on October 29, 2001, at 10:44:20
> As I said, I wasn't able to find out the Kd for modafinil (despite my not-so-vast resources) and I was wondering if you knew it or any other relevant information.
Hi Elizabeth.Since you really, *really* want some info, I fired-up a few neurons and put some things together for you. It's the least I could do for someone so genuinely helpful. I hope it helps.
The statements appearing in the package insert you cited certainly are consistent with a dopaminomimetic agent. However, based upon my reading, I would guess it possible that the euphoriant and reinforcing properties of modafinil are the result of its ability to promote glutamatergic neurotransmission along pathways afferent to the nucleus accumbens.
From what little I've read of modafinil, I would say that:
1. The wakefullness-promoting effects are produced via increased release of glutamate in the hypothalamus.
2. Euphoriant effects and increased vigilence are produced via increased release of glutamate in the thalamus and hippocampus.
3. For both phenomena, it might be that the balance of glutamatergic to GABAergic activity in these areas is pushed towards the former and causes a sort of disinhibition upon reticular and limbic pathways respectively.
Please see:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9759978&dopt=Abstract
That's about the best I can do for you at this point.
This might be of some help:
http://www.nevapress.com/cnsdr/full/5/3/193.pdf
Perhaps adrafinil possesses DAergic properties that modafinil does not. From the personal experiences described by people on Psycho-Babble, it would seem that adrafinil is different enough from its metabolite (modafinil) to be considered separately. I don't believe either one acts as a NE alpha-1 agonist as was once thought.
I'd be curious to see what conclusions you come up with regarding modafinil. I would be happy to discover it to be a DA reuptake inhibitor. Some of the studies showing it to spare DA terminals of the toxic effects of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) might suggest a direct effect. I don't know. However, the authors of the following study state that this is not the result of DA reuptake inhibition.
Maybe when I get well, I'll have the brain power to figure some of this stuff out. I guess I'll just keep praying. In the meantime, feel free to pester your S.O. to lend us some of his.
Also...I don't have ready access to medical journals, but perhaps you'll find the following citation useful. No abstract was available on Medline. Even so, this would represent but one study. It would be nice to see a bunch of corraborating investigations assaying DAT affinity.
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Sleep 1994 Aug;17(5):436-7 Related Articles, Books, LinkOut
Modafinil binds to the dopamine uptake carrier site with low affinity.Mignot E, Nishino S, Guilleminault C, Dement WC.
Stanford Sleep Disorders Center, Palo Alto, California.
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Take care.- Scott
poster:SLS
thread:81334
URL: http://www.dr-bob.org/babble/20011025/msgs/82600.html