Review article: effects of the 5-HT3 receptor antagonist alosetron on neuromuscular transmission in canine and human intestinal muscle

Background: Currently, therapeutic treatments for irritable bower syndrome fail to produce significant clinical results. We hypothesized that alosetro n, a selective 5-HT3 antagonist, may provide symptomatic relief in irritabl e bowel syndrome patients through a decrease in the amplitude of gastrointe stinal contractions. Aim: To determine the in vitro effect of alosetron on neuromuscular transmi ssion in the canine and human jejunal and colonic muscularis externa, Results: Alosetron diminished electrical field-stimulated (EFS) contraction s recorded from muscles of the canine and human small and large intestines. Mechanistically, the diminished EFS response could be explained by the abi lity of alosetron to decrease the fractional release of C-14-choline radiol abelled acetylcholine evoked by EFS from human jejunal muscle, The inhibiti on of EFS contractions was not limited to atropine-sensitive events, as non -cholinergic excitatory EFS evoked contractions were also inhibited. Additi onally, alosetron at high concentrations (> 30 mu M) directly altered betha nechol stimulated contractions. Conclusion: Caution must be used in the interpretation of these data becaus e significant alterations in EFS-induced contractions were only observed wi th large pharmacological concentrations of alosetron, and the response was not selective for cholinergically-mediated excitatory neuromuscular transmi ssion.