Alosetron, a 5-HT3 receptor antagonist, delays colonic transit in patients with irritable bowel syndrome and healthy volunteers

Aliment Pharmacol Ther. 2000 Jun;14(6):775-82. doi: 10.1046/j.1365-2036.2000.00762.x.

Abstract

Background: Alosetron is a potent and selective 5-HT3 receptor antagonist, which has been shown to be beneficial in the treatment of female patients with non-constipated irritable bowel syndrome.

Aims: To investigate the effect of alosetron on whole gut, small bowel and colonic transit in patients with irritable bowel syndrome (Study 1) and healthy volunteers (Study 2).

Subjects: Thirteen patients with irritable bowel syndrome and 12 healthy volunteers.

Methods: Both studies were randomized, double-blind, placebo-controlled with a two-way crossover design, in which each subject received alosetron (2 mg b.d. administered orally) or placebo for 8 days. Mean whole gut transit was determined from the excretion of radio-opaque markers; small bowel transit was determined from rise in breath hydrogen after a meal; and colonic transit and segmental transit were evaluated from abdominal X-ray. In addition, colonic transit was calculated by subtracting small bowel transit time from whole gut transit time.

Results: Alosetron increased colonic transit time by prolonging left colonic transit in both patients with irritable bowel syndrome and controls. This resulted in a tendency for the whole gut transit to be delayed in irritable bowel syndrome patients (P=0.128), which was confirmed in controls (P=0.047).

Conclusion: Alosetron delays colonic transit by prolonging left colonic transit. These results add to the body of evidence suggesting that alosetron should have a therapeutic role in patients with non-constipated irritable bowel syndrome.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carbolines / pharmacology*
  • Carbolines / therapeutic use
  • Colon / drug effects
  • Colon / physiology
  • Colonic Diseases, Functional / drug therapy*
  • Colonic Diseases, Functional / pathology
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Gastrointestinal Transit / drug effects*
  • Humans
  • Intestine, Small / drug effects
  • Intestine, Small / physiology
  • Male
  • Middle Aged
  • Serotonin Antagonists / pharmacology*
  • Serotonin Antagonists / therapeutic use

Substances

  • Carbolines
  • Serotonin Antagonists
  • alosetron