Clinical neuropharmacology
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Clin Neuropharmacol · Jan 1993
Randomized Controlled Trial Comparative Study Clinical TrialDownregulation of serotonin receptor subtypes by nortriptyline and adinazolam in major depressive disorder: neuroendocrine and platelet markers.
Neuroendocrine and platelet markers of serotonin (5-hydroxytryptamine, 5-HT) receptor functioning are useful tools for studying the downregulation of 5-HT receptors, a leading hypothesis for the mechanism of action of antidepressant drugs. The 5-HT releaser fenfluramine raises body temperature as well as plasma concentrations of ACTH, cortisol, and prolactin. Pretreatment with the 5-HT1 antagonist pindolol did not block the hyperthermic response to fenfluramine, mediating its actions via non-5-HT1 receptor subtypes (presumably 5-HT2/1C). ⋯ IC50 values for ketanserin inhibition of 5-HT-induced platelet shape change response, a marker of 5-HT2/1c receptors, were elevated after nortriptyline treatment in depressed patients, and this increase could be accounted for by those subjects who responded well to antidepressant treatment. Adinazolam treatment did not alter the platelet shape change response. Our data suggest that downregulation of 5-HT2/1c receptors may be linked to the clinical response of depressed patients treated with nortriptyline.