A novel 5-HT3 receptor agonist, YM-31636, increases gastrointestinal motility without increasing abdominal pain.

Abstract

We examined the effects of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate), a novel 5-HT3 receptor agonist, on gastrointestinal functions including visceral pain reflex in rats. Injection of YM-31636 increased the number of fecal pellets. This effect was completely inhibited by ramosetron, a 5-HT3 receptor antagonist. YM-31636 also increased the intracolonic pressure measured in both conscious and anesthetized rats. In isolated distal colon, YM-31636 increased the short-circuit current response. This effect was abolished by ramosetron. Both the maximal response and the potency of YM-31636 were weaker than those of other 5-HT3 receptor agonists. In two visceral pain reflex models, YM-31636 neither changed the magnitude of pressor response to colonic distension in anesthetized rats nor affected the visceromotor threshold to colorectal distension in conscious rats. In conclusion, YM-31636 facilitated defecation without increasing visceral pain. Consequently, 5-HT3 receptor agonists like YM-31636 would be promising in the treatment of chronic constipation.

• Authors: T Kiso, H Ito, K Miyata, T Kamato, Y Naitoh, K Iwaoka, T Yamaguchi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 431 Issue 1 Pg. 35-41 (Nov 09 2001) ISSN: 0014-2999 [Print] Netherlands
• PMID: 11716840 (Publication Type: Journal Article)

Chemical References

• 2-(1H-imidazol-4-ylmethyl)-8H-indeno(1,2-d)thiazole
• Benzimidazoles
• Pyrroles
• Serotonin Antagonists
• Serotonin Receptor Agonists
• Thiazoles
• Water
• ramosetron

Topics

• Abdominal Pain
• Animals
• Benzimidazoles (pharmacology)
• Colon (drug effects, innervation)
• Defecation (drug effects)
• Gastrointestinal Motility (drug effects)
• Intestinal Mucosa (drug effects)
• Male
• Pressure
• Pyrroles (pharmacology)
• Rats
• Rats, Wistar
• Reflex, Abdominal (drug effects)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)
• Thiazoles (pharmacology)
• Water (metabolism)