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

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• 作者：Kiso ; Tetsuo ; Ito ; Hiroyuki ; Miyata ; Keiji ; Kamato ; Takeshi ; Naitoh ; Yuki ; Iwaoka ; Kiyoshi ; Yamaguchi ; Tokio
• 关键词：YM-31636 ; 5-HT₃ receptor agonist ; Visceral pain ; Constipation ; Defecation ; Short-circuit current
• 刊名：European Journal of Pharmacology
• 出版年：2001
• 出版时间：November 9, 2001
• 年：2001
• 卷：431
• 期：1
• 页码：35-41
• 全文大小：141 K

文摘

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.