Is the action of cisapride on the guinea-pig ileum mediated via 5-HT4 receptors?

Eur J Pharmacol. 1992 Feb 25;212(1):51-9. doi: 10.1016/0014-2999(92)90071-b.


It has been suggested that benzamides, like cisapride, exert their effects on the guinea-pig ileum via activation of a 5-HT receptor (5-HT4 receptor?) mechanism. The aim of this study was to determine whether an how the 5-HT4 receptor (previously described in mouse colliculi neurones) is involved in the cisapride-induced effect. The effects induced by cisapride were compared with those of 5-hydroxytryptamine (5-HT) and 5-methoxytryptamine (5-MeOT) either alone or in the presence of a 5-HT4 antagonist (micromolar concentration of ICS 205-930) or a benzamide antagonist (R 50 595). As a model we used the electrically stimulated longitudinal muscle myenteric plexus preparation from the guinea-pig ileum. Cisapride (3.10(-7) M), 5-HT and a 5-HT4 receptor agonist 5-MeOT (3.10(-10)-10(-6) M) induced similar effects, i.e. enhancement of the twitch responses. After rinsing the organ baths, a second addition of the agonists resulted in a similar response. The studied agonists showed mutual desensitization. Cisapride desensitized the response induced by 5-HT or 5-MeOT, and 5-MeOT or 5-HT desensitized the effect induced by cisapride. In preparations preincubated with a 5-HT4 receptor antagonist, ICS 205-930- (3.10(-6) M) or R 50 595 (3.10(-7) M), a benzamide with a specific antagonistic action on the effect induced by 5-HT and benzamides on the guinea-pig ileum, the effects induced by cisapride, 5-HT and 5-MeOT were abolished. These results indicate that cisapride indeed exerts its effect via an agonistic action on a serotonin receptor, probably the previously described 5-HT4 receptor.

MeSH terms

  • 5-Methoxytryptamine / pharmacology*
  • Animals
  • Cisapride
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Guinea Pigs
  • Ileum / drug effects*
  • Ileum / physiology
  • In Vitro Techniques
  • Indoles / administration & dosage
  • Indoles / pharmacology*
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Receptors, Serotonin / metabolism*
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology*
  • Tropisetron


  • Indoles
  • Piperidines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • R 50595
  • Serotonin
  • 5-Methoxytryptamine
  • Tropisetron
  • Cisapride