ONDANSETRON FACILITATES NEUROMUSCULAR-TRANSMISSION IN THE GUINEA-PIG ILEUM

The effects of ondansetron on the neuromuscular function of the guinea -pig ileum were investigated in vitro. Ondansetron, but not tropisetro n or MDL 72222 (1 alpha-H-3 alpha-5 alpha-H-tropan-3-yl-3,5-dichlorobe nzoate), enhanced submaximal electrically induced contractions (EC50 = 1.3 x 10(-5) M). Desensitization with 5-hydroxytryptamine (I x 10(-5) M) or 2-methyl-5-HT (1 x 10(-5) M) abolished this facilitatory respon se, which remained unaltered after desensitization with 5-methoxytrypt amine (1 x 10(-5) M) or addition of tropisetron, MDL 72222, N-acetyl-5 -hydroxytryptophyl-5-hydroxytryptophan, SB203186 (1-piperidinylethyl-1 H-indole-3 carboxylate hydrochloride), pirenzepine or hexamethonium. A t higher concentrations, ondansetron decreased the electrically induce d contractions (EC50 = 1 x 10(-4) M); the inhibitory response was unaf fected by (-)-naloxone (1 x 10(-6) M) or idazoxan (1 x 10(-6) M). We c onclude that, in the guinea-pig ileum, ondansetron elicits a biphasic response: facilitation of neuromuscular transmission mediated by a ser otonergic receptor distinct from the 5-HT3, 5-HT4 or putative 5-HT1P r eceptors, and an inhibitory response that does not involve opiate or a lpha(2)-adrenoceptors.