Pharmacological profile of YM-31636, a novel 5-HT3 receptor agonist, in vitro

European Journal of Pharmacology
H ItoT Yamaguchi

Abstract

We investigated the in vitro pharmacological profile of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate). In cloned human 5-HT3A receptors, YM-31636 had a pKi value of 9.67 vs. ramosetron and pKi values for other 5-HT3 receptor agonists were less than 7. YM-31636 showed very low affinities for other receptors. YM-31636 induced contraction of isolated guinea pig distal colon. The intrinsic activity was approximately 0.90 compared with 5-hydroxytryptamine's (5-HT) 1.0, and the potency was 26 times greater than that of 5-HT. YM-31636 increased short-circuit current (Isc) in the isolated guinea pig distal colon. In this case, the relative intrinsic activity was approximately 0.19. In isolated guinea pig right atrium, YM-31636 induced tachycardia with the relative intrinsic activity of approximately 0.23. All these effects of YM-31636 were antagonized by ramosetron, a selective 5-HT3 receptor antagonist. These results suggest that YM-31636 is a potent and selective 5-HT3 receptor agonist, preferentially acting on the contraction of the colon.

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Citations

Jul 11, 2002·Life Sciences·Yukinori NagakuraTokio Yamaguchi
Jun 20, 2001·Bioorganic & Medicinal Chemistry Letters·M DukatR A Glennon
Jun 6, 2003·Bioorganic & Medicinal Chemistry·Pedro Luis López-TudancaAurelio Orjales
Sep 18, 2003·Bioorganic & Medicinal Chemistry·Richard A GlennonHasan Syed
Jul 9, 2004·Clinical and Experimental Pharmacology & Physiology·Yang NingHsiao Chang Chan
Mar 25, 2005·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·K KawanoT Shishikura
Oct 27, 2004·Pharmacology & Therapeutics·Takafumi NagatomoTadazumi Komiyama
Dec 5, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anders J SmithHui Dong

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