The pharmacological properties of the novel selective 5-HT3 receptor antagonist, alosetron, and its effects on normal and perturbed small intestinal transit in the fasted rat

Neurogastroenterol Motil. 1999 Jun;11(3):207-17. doi: 10.1046/j.1365-2982.1999.00148.x.


The purpose of this study was to investigate the pharmacological properties of the novel, selective 5-HT3 receptor antagonist, alosetron, and its effects on transit time in both the normal and perturbed small intestine of the rat. Alosetron concentration-dependently inhibited radioligand binding in membranes containing rat and human 5-HT3 receptors with estimated pKi values of 9.8 (n = 3) and 9.4 (n = 6), respectively. In selectivity studies alosetron had little or no significant affinity for any of the many other receptors and ion channels studied. Alosetron potently antagonized the depolarization produced by 5-HT in the rat vagus nerve (estimated pKB value of 9.8, n = 25). In anaesthetized rats, i. v. administration of alosetron inhibited 2-methyl-5-HT induced bradycardia (Bezold Jarisch index) at 1 and 3 microg kg-1, with an agonist dose ratio of approximately 3.0 at 1.0 microg kg-1, = 3-5). Alosetron administered via the duodenum also inhibited this reflex, with duration of action that was significantly longer than that seen with ondansetron (120-60 min, respectively, n = 6). Alosetron had no significant effect on normal small intestinal propulsion in the rat, but fully reversed the increase in intestinal propulsion (96%, n = 3) produced by egg albumin challenge. Alosetron is a highly selective 5-HT3 antagonist which normalizes perturbed small intestinal propulsion. Previous clinical data in IBS patients together with the transit data provide a good rationale for further studies with alosetron in IBS patients.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Carbolines / therapeutic use*
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Drug Evaluation, Preclinical
  • Fasting*
  • Gastrointestinal Transit / drug effects*
  • Intestine, Small / drug effects*
  • Ondansetron / pharmacology
  • Ovalbumin / pharmacology
  • Radioligand Assay
  • Rats
  • Reference Values
  • Reflex / drug effects
  • Serotonin Antagonists / therapeutic use*
  • Vagus Nerve / drug effects


  • Adrenergic alpha-Agonists
  • Carbolines
  • Serotonin Antagonists
  • alosetron
  • Ondansetron
  • apraclonidine
  • Ovalbumin
  • Clonidine