Clomipramine enhances the cortisol response to 5-HTP: implications for the therapeutic role of 5-HT2 receptors.
We measured the cortisol response to the 5-HT precursor, 5-hydroxytryptophan, (5-HTP) in seven patients with major depression before and after 8 weeks treatment with the tricyclic antidepressant, clomipramine. The cortisol response to 5-HTP was significantly increased following clomipramine treatment, suggesting that clomipramine, like selective serotonin re-uptake inhibitors (SSRIs), enhances this 5-HT2 receptor mediated response. Because other tricyclic antidepressants do not increase 5-HTP-mediated cortisol release, it seems unlikely that enhancement of 5-HT2 receptor function is a critical mechanism for antidepressant action. However, facilitation of neurotransmission at 5-HT2 receptors could account for the efficacy of clomipramine and SSRIs in the treatment of obsessive compulsive disorder and also for their liability to cause orgasmic dysfunction.
Sargent
P A
PA
University Department of Psychiatry, Warneford Hospital, Oxford, UK.
Quested
D J
DJ
Cowen
P J
PJ
D006916:5-Hydroxytryptophan / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D002997:Clomipramine / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011985:Receptors, Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D006916:5-Hydroxytryptophan; D002997:Clomipramine; D006854:Hydrocortisone; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors