Interaction between antidepressants and phosphoinositide signal transduction system in human platelets

Moshe Rehavi, Zohara Jerushalemi, Alex Aviv, Nathaniel Laor, Eduard Podliszewski, Leon Karp, Sara Shavit, Ronit Weizman

Research output: Contribution to journalArticlepeer-review

Abstract

the present study was designed to evaluate the inhibitory effect of antidepressants on thrombin-induced phosphoinositide (PI) hydrolysis. Thrombin 5 units/ml induced a 100%-200% increase in platelet inositol phosphates (IPs) formation. This effect was inhibited in a dose-dependent manner by various heterocyclic antidepressants (IC50 40-170 μmol/L) The monoamine oxidase inhibitor, phenelzine, in concentrations up to 500 μmol/L, was devoid of inhibitory activity. the tricyclic antidepressants, (50 μmol/L) inhibited also thrombin-induced platelet aggregation by 32%-47%. No alteration in thrombin-induced IPs formation was detected in recovered major depressed patients (n = 15) maintained on clomipramine (75-150 mg/day). These results indicate that the heterocyclic antidepressants interfere with the thrombin-linked PI-signaling system. However, the inhibitory effect is achieved only in concentrations above the plasma concentrations obtained with therapeutic doses of these agents.

Original languageEnglish
Pages (from-to)40-44
Number of pages5
JournalBiological Psychiatry
Volume33
Issue number1
DOIs
StatePublished - 1 Jan 1993

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