The Selective 5-Hydroxytryptamine (5-HT)4-Receptor Agonist RS67506 Enhances Lower Intestinal Propulsion in Mice

The Japanese Journal of Pharmacology

Keiji Miyata¹  Hiroyuki Ito¹  Yukinori Nagakura¹  Tetsuo Kiso¹  Yuki Naitoh¹ 

[1] Neuroscience Research, Pharmacological Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

关键词: 5-HT3 receptor;    5-HT4 receptor;    RS67506;   

DOI  :  10.1254/jjp.74.209

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(15)Cited-By(5)Interactions of gastrointestinal prokinetic benzamides with 5-hydroxytryptamine (5-HT)3 and 5-HT4 receptors and the relation to their effects on gastrointestinal propulsion were investigated. Renzapride and zacopride potently inhibited 5-HT3-receptor-mediated contractions in the guinea pig colon, whereas RS67506 (1-(4-amino-5-chloro-2-methoxyphenyl)-3-[1-(2-methyl sulphonylamino)ethyl-4-piperidinyl]-1-propanone hydrochloride), a selective 5-HT4-receptor agonist, showed no inhibition. RS67506, renzapride and zacopride all exerted 5-HT4 receptor-mediated relaxation in the carbachol-precontracted rat oesophagus. In mice, RS67506 shortened the whole gut transit time, whereas renzapride and zacopride were reported to prolong it. Gastrointestinal prokinetic benzamides, which are selective for 5-HT4-receptor agonistic over 5-HT3-receptor antagonistic action, may be useful in treating gastrointestinal disorders associated with impaired lower intestinal propulsion such as constipation.

【 授权许可】

Unknown