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

We examined the effects of YM-31636 (2-(1 H -imidazol-4-ylmethyl)-8 H -inde no[1,2-d]thiazole monofumarate), a novel 5-HT3 receptor agonist, on gastroi ntestinal functions including visceral pain reflex in rats. Injection of YM -31636 increased the number of fecal pellets. This effect was completely in hibited 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 re sponse. 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 no r affected the visceromotor threshold to colorectal distension in conscious rats. In conclusion, YM-31636 facilitated defecation without increasing vi sceral pain. Consequently, 5-HT3 receptor agonists like YM-31636 would be p romising in the treatment of chronic constipation. (C) 2001 Elsevier Scienc e B.V. All rights reserved.