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modafinil » SLS

Posted by zeugma on September 21, 2005, at 5:12:59

In reply to Re: Caffeine Partially Counteracts Sedationfrom Ambien » jrbecker, posted by SLS on September 20, 2005, at 23:12:03

Would you happen to know if there is any connection between orexin/hypocretin and HPA axis activity? Perhaps chronic low orexin leads to increased HPA activity and increased cortisol production? I'm really reaching on this one.>>

Orexin is crucially involved in HPA function:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11106974&query_hl=2

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11830283&query_hl=6

It seems from reading these abstracts that the HPA axis is activated by orexin, but possibly a orexin deficiency in orexin could cause a compensatory rise in HPA activity from some other source.

Modafinil is being used as a treatment for substance abuse:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15525998&query_hl=7

Modafinil's activation of orexin receptors appears to be secondary to its ability to release histamine (the orexinergic system is activated by histamine). I would bet that modafinil's actions on histamine are responsible for a lot of its side effects, as well as its therapeutic action. Modafinil strongly activates the tuberomammillary nucleus, which is the site of all histamine projections in the brain.

My pdoc claims that modafinil's primary action is on histamine.

-z


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URL: http://www.dr-bob.org/babble/20050921/msgs/557581.html