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Re: provigil discussion » zeugma

Posted by SLS on February 26, 2006, at 14:38:46

In reply to Re: provigil discussion » SLS, posted by zeugma on February 26, 2006, at 12:50:20

> the mechanisms by which modafinil improves depression (usually implemented as an augmenting agent) might involve the shifting of thalamic glutamate/GABA balance towards glutamate and the subsequent activation of DA neurons in the nucleus accumbens.>>
>
> Modafinil also elevates serotonin levels in cortex and dorsal raphe, which is surely relevant to depression.
>
> -z


I did not know this. Do you think this is an effect secondary to another mechanism of action of modafinil, or does the molecule affect 5-HT neurons directly? In other words, are the outflows of 5-HT in these areas secondary to increases in the releases of hypocretin or glutamate produced elsewhere by modafinil?

Again, we see hypocretin:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12417670&query_hl=19&itool=pubmed_docsum

I found this interesting:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15668907&query_hl=14&itool=pubmed_docsum

Here, modafinil seems to act as an amplifier. By itself, though, it does not elicit 5-HT increase. I noticed some other work by these same authors suggesting otherwise, but at concentrations too high to be relevant to those in clinical use.


- Scott

 

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