G. Audolfsson et al., Review article: effects of the 5-HT3 receptor antagonist alosetron on neuromuscular transmission in canine and human intestinal muscle, ALIM PHARM, 13, 1999, pp. 39-47
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.