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 bowel syndrome fail to produce significant clinical results. We hypothesized that alosetron, a selective 5-HT3 antagonist, may provide symptomatic relief in irritable bowel syndrome patients through a decrease in the amplitude of gastrointestinal contractions.


OBJECTIVE
To determine the in vitro effect of alosetron on neuromuscular transmission in the canine and human jejunal and colonic muscularis externa.


RESULTS
Alosetron diminished electrical field-stimulated (EFS) contractions recorded from muscles of the canine and human small and large intestines. Mechanistically, the diminished EFS response could be explained by the ability of alosetron to decrease the fractional release of 14C-choline radiolabelled acetylcholine evoked by EFS from human jejunal muscle. The inhibition of EFS contractions was not limited to atropine-sensitive events, as non-cholinergic excitatory EFS evoked contractions were also inhibited. Additionally, alosetron at high concentrations (> 30 microM) directly altered bethanechol stimulated contractions.


CONCLUSIONS
Caution must be used in the interpretation of these data because significant alterations in EFS-induced contractions were only observed with large pharmacological concentrations of alosetron, and the response was not selective for cholinergically-mediated excitatory neuromuscular transmission.
Audolfsson
G
G
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Bayguinov
O
O
Yamamoto
T
T
Somogyi
G T
GT
Schraut
W H
WH
Sanders
K M
KM
Bauer
A J
AJ
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D004285:Dogs; D004594:Electrophysiology; D006801:Humans; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D002243:Carbolines; D012702:Serotonin Antagonists; C090840:alosetron; D002794:Choline