Downregulation of serotonin receptor subtypes by nortriptyline and adinazolam in major depressive disorder: neuroendocrine and platelet markers.

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Stahl SM, Hauger RL, Rausch JL, Fleishaker JC, Hubbell-Alberts E

Downregulation of serotonin receptor subtypes by nortriptyline and adinazolam in major depressive disorder: neuroendocrine and platelet markers.

Clin Neuropharmacol. 1993;16 Suppl 3:S19-31.

PubMed ID

8131152 [ View in PubMed

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Abstract

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). We observed blunted hyperthermic responses to fenfluramine in unmedicated patients with major depressive disorder. We also observed that the neuroendocrine responses to fenfluramine were decreased by chronic treatment with the tricyclic antidepressant nortriptyline but not by chronic treatment with tricyclic antidepressant nortriptyline but not by chronic treatment with adinazolam, a triazolobenzodiazepine with purported antidepressant activity. 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Nortriptyline	5-hydroxytryptamine receptor 2C	Protein	Humans	Unknown	Antagonist Downregulator	Details

Pharmaco-metabolomics

Drug	Drug Groups	Metabolite	Change	Description
Fenfluramine	Approved Illicit Investigational Withdrawn	Cortisol	increased	Fenfluramine increases the level of Cortisol in the blood

Pharmaco-proteomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Nortriptyline	Approved	HTR2C	3358	decreased	Nortriptyline results in decreased expression of HTR2C protein	Xq23