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.
|Number of pages||4|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - Jun 1998|
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