The selective 5-hydroxytryptamine (5-HT)4-receptor agonist RS67506 enhances lower intestinal propulsion in mice

Jpn J Pharmacol. 1997 Jun;74(2):209-12. doi: 10.1254/jjp.74.209.


Interactions of gastrointestinal prokinetic benzamides with 5-hydroxytryptamine (5-HT)3 and 5-HT4 receptors and the relation to their effects on gastrointestinal propulsion were investigated. Renzapride and zacopride potently inhibited 5-HT3-receptor-mediated contractions in the guinea pig colon, whereas RS67506 (1-(4-amino-5-chloro-2-methoxyphenyl)-3-[1-(2-methyl sulphonylamino)ethyl-4-piperidinyl]-1-propanone hydrochloride), a selective 5-HT4-receptor agonist, showed no inhibition. RS67506, renzapride and zacopride all exerted 5-HT4 receptor-mediated relaxation in the carbachol-precontracted rat oesophagus. In mice, RS67506 shortened the whole gut transit time, whereas renzapride and zacopride were reported to prolong it. Gastrointestinal prokinetic benzamides, which are selective for 5-HT4-receptor agonistic over 5-HT3-receptor antagonistic action, may be useful in treating gastrointestinal disorders associated with impaired lower intestinal propulsion such as constipation.

MeSH terms

  • Animals
  • Colon / drug effects
  • Esophagus / drug effects
  • Gastrointestinal Motility / drug effects*
  • Gastrointestinal Transit / drug effects
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred ICR
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT4
  • Serotonin Receptor Agonists / pharmacology*
  • Sulfonamides / pharmacology*


  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Sulfonamides
  • Receptors, Serotonin, 5-HT4
  • RS 67506