The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients

Aliment Pharmacol Ther. 2002 Jul;16(7):1357-66. doi: 10.1046/j.1365-2036.2002.01287.x.


Aim: To conduct a placebo-controlled functional brain imaging study to assess the effect of the 5-hydroxytryptamine-3 receptor antagonist, alosetron, on irritable bowel syndrome symptoms, regional brain activation by rectosigmoid distension and associated perceptual and emotional responses.

Methods: Fifty-two non-constipated irritable bowel syndrome patients (28 female) were enrolled in a randomized, placebo-controlled trial with alosetron (1-4 mg b.d.). Thirty-seven patients completed both brain scans following randomization. Rectosigmoid stimulation was performed with a computer-controlled barostat. Changes in regional cerebral blood flow were assessed using H215O positron emission tomography. Stimulus ratings and changes in gastrointestinal symptoms were assessed using verbal descriptor scales.

Results: Alosetron, but not placebo, treatment was associated with a decrease in symptom ratings, and reductions in emotional stimulus ratings. Compared to baseline, alosetron treatment was associated with reduced regional cerebral blood flow in bilateral frontotemporal and various limbic structures, including the amygdala. Compared to placebo, decreases in activity of the amygdala, ventral striatum, hypothalamus and infragenual cingulate gyrus were significantly greater after alosetron.

Conclusions: In non-constipated irritable bowel syndrome patients, 3 weeks of treatment with a 5-hydroxytryptamine-3 receptor antagonist decreases brain activity in response to unanticipated, anticipated and delivered aversive rectal stimuli in structures of the emotional motor system, and this is associated with a decrease in gastrointestinal symptoms.

Publication types

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

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / physiopathology
  • Brain Chemistry
  • Carbolines / pharmacology*
  • Carbolines / therapeutic use
  • Cerebrovascular Circulation / drug effects
  • Colonic Diseases, Functional / diagnostic imaging
  • Colonic Diseases, Functional / drug therapy
  • Colonic Diseases, Functional / physiopathology*
  • Double-Blind Method
  • Female
  • Gastrointestinal Agents / pharmacology*
  • Gastrointestinal Agents / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Nociceptors / drug effects
  • Nociceptors / physiopathology
  • Physical Stimulation / methods
  • Receptors, Serotonin / analysis
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin, 5-HT3
  • Rectum / physiopathology
  • Serotonin Antagonists / pharmacology*
  • Serotonin Antagonists / therapeutic use
  • Tomography, Emission-Computed
  • Treatment Outcome


  • Carbolines
  • Gastrointestinal Agents
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • alosetron