Investigation of the effects of YM-31636, a novel 5-HT3 receptor agonist, on defecation in normal and constipated ferrets.

Abstract

We examined the effects of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate), a newly synthesized 5-HT(3) receptor agonist, on defecation in normal and constipated ferrets, and evaluated it as an agent against constipation. YM-31636 facilitated defecation without inducing diarrhea or emetic episodes. This effect occurred within 1 h after oral administration, mostly within 30 min, whereas sodium picosulfate, a widely used laxative, tended to increase the frequency of defecation for several hours with much lower peak incidence than that of YM-31636, and induced diarrhea. UK14304 (brimonidine), an alpha2 receptor agonist, and morphine reduced the frequency of defecation and YM-31636 restored it. These effects of YM-31636 were antagonized by ramosetron, a 5-HT(3) receptor antagonist. These results suggest that YM-31636 could be promising in the treatment of constipation. Because of an early and reliable onset of action compared with sodium picosulfate, YM-31636 could make it easier to control the time of defecation.

• Authors: H Ito, T Kiso, H Yuki, Y Naitoh, K Miyata, K Iwaoka, T Yamaguchi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 424 Issue 2 Pg. 151-7 (Jul 20 2001) ISSN: 0014-2999 [Print] Netherlands
• PMID: 11476761 (Publication Type: Journal Article)

Chemical References

• 2-(1H-imidazol-4-ylmethyl)-8H-indeno(1,2-d)thiazole
• Citrates
• Organometallic Compounds
• Picolines
• Pyrroles
• Serotonin Receptor Agonists
• Thiazoles
• Water
• picosulfate sodium

Topics

• Animals
• Citrates
• Constipation (physiopathology)
• Defecation (drug effects)
• Dose-Response Relationship, Drug
• Feces
• Ferrets
• Male
• Nausea (chemically induced)
• Organometallic Compounds
• Picolines (pharmacology)
• Pyrroles (adverse effects, pharmacology)
• Serotonin Receptor Agonists (adverse effects, pharmacology)
• Thiazoles (adverse effects, pharmacology)
• Time Factors
• Vomiting (chemically induced)
• Water (metabolism)