Trazodone is a potent agonist at 5-HT(2C) receptors mediating inhibition of the N-methyl-D-aspartate/nitric oxide/cyclic GMP pathway in rat cerebellum

Manuela Marcoli, Guido Maura, Massimo Tortarolo, Maurizio Raiteri

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of trazodone on the cyclic GMP elevation elicited by N- methyl-D-aspartate in rat cerebellar slices were analyzed. Trazodone inhibited in a concentration-dependent manner (EC50 = 0.82 nM) the cyclic GMP response evoked by 0.1 N-methyl-D-aspartate. The inhibition was near complete at 10 nM trazodone. The effect of 10 nM trazodone was unaffected by 0.3 μM spiperone or rauwolscine, antagonists with selectivity for the 5- HT(serotonin)(2A) or the 5-HT(2B) subtype, respectively, but it was totally prevented by 0.01 μM mesulergine, a 5-HT(2A)/5-HT(2B)/5-HT(2C) receptor antagonist. Trazodone was potently counteracted (IC50 = 2.7 nM) by the selective 5-HT(2B)/5-HT(2C) receptor antagonist N-(1-methyl-5-indolyl)-N-(3- pyridil) urea HCl and, less potently (IC50 = 95 nM), by ketanserin, a 5- HT(2A)/5-HT(2C) receptor blocker. It is concluded that trazodone behaves as a potent full agonist at the 5-HT(2C) receptor mediating inhibition of the cerebellar N-methyl-D-aspartate/nitric oxide/cyclic GMP system.

Original languageEnglish
Pages (from-to)983-986
Number of pages4
JournalJournal of Pharmacology and Experimental Therapeutics
Volume285
Issue number3
Publication statusPublished - Jun 1998

ASJC Scopus subject areas

  • Pharmacology

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