PT  - JOURNAL ARTICLE
AU  - Manuela Marcoli
AU  - Guido Maura
AU  - Massimo Tortarolo
AU  - Maurizio Raiteri
TI  - Trazodone is a Potent Agonist at 5-HT<sub>2C</sub> Receptors Mediating Inhibition of the N-Methyl-<span class="sc">d</span>-Aspartate/Nitric Oxide/Cyclic GMP Pathway in Rat Cerebellum
DP  - 1998 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 983--986
VI  - 285
IP  - 3
4099  - http://jpet.aspetjournals.org/content/285/3/983.short
4100  - http://jpet.aspetjournals.org/content/285/3/983.full
SO  - J Pharmacol Exp Ther1998 Jun 01; 285
AB  - 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 μM 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-HT2B subtype, respectively, but it was totally prevented by 0.01 μM mesulergine, a 5-HT2A/5-HT2B/5-HT2C receptor antagonist. Trazodone was potently counteracted (IC50 = 2.7 nM) by the selective 5-HT2B/5-HT2C receptor antagonist N-(1-methyl-5-indolyl)-N-(3-pyridil) urea HCl and, less potently (IC50 = 95 nM), by ketanserin, a 5-HT2A/5-HT2C receptor blocker. It is concluded that trazodone behaves as a potent full agonist at the 5-HT2C receptor mediating inhibition of the cerebellar N-methyl-d-aspartate/nitric oxide/cyclic GMP system. The American Society for Pharmacology and Experimental Therapeutics