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Re: could nefazodone get any more peculiar? iforgotmypassword

Posted by jrbecker76 on December 29, 2008, at 18:45:49

In reply to could nefazodone get any more peculiar?, posted by iforgotmypassword on December 28, 2008, at 17:39:22

> "Nefazodone significantly increased plasma levels of prolactin (PRL) and raised oral temperature. There was also a trend towards an increase in plasma cortisol. These results are consistent with an acute facilitatory effect of some aspects of 5-HT neurotransmission, perhaps mediated through nefazodone's metabolism to its major metabolite, m-chlorophenylpiperazine (mCPP)."
> this may be wrong, i was under the impression that a 5-HT2a antagonistic mechanism would lower cortisol, so i am thinking either the mCPP metabolite much more significant than imagined, or the drug is much messier than it already looks. and prolactin...?

chronic treatment should reverse this....

: J Clin Psychopharmacol. 1994 Aug;14(4):268-73.Links
Attenuation of the prolactin-stimulating and hyperthermic effects of nefazodone after subacute treatment.
Walsh AE, Cowen PJ.

MRC Unit of Clinical Pharmacology, Littlemore Hospital, Oxford, United Kingdom.

The acute administration of the antidepressant drug nefazodone (100 mg orally) to healthy male volunteers increased prolactin concentrations in plasma and elevated oral temperature. After repeated treatment with 100 mg of nefazodone twice daily for 7 days, these effects were attenuated. We propose that the ability of nefazodone given acutely to increase prolactin concentrations and oral temperature is mediated via metabolism to the 5-hydroxytryptamine1C (5-HT1C) receptor agonist meta-chlorophenylpiperazine. The attenuation of these effects after subacute treatment could be due to an adaptive down-regulation of 5-HT1C receptors or to direct blockade of 5-HT1C receptors by nefazodone and its metabolite hydroxynefazodone (OH-nefazodone), the concentrations in plasma of which increase substantially during the 7-day treatment period.




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