Effects of Mosapride Citrate, a 5-HT4 Receptor Agonist, on Colonic Motility in Conscious Guinea Pigs

The Japanese Journal of Pharmacology

Takashi Yoshikawa²  Naoyuki Yoshida²  Ryuji Nagai³  Atsuko Inui¹  Tsugutaka Ito¹ 

[1] Department of Safety Pharmacology, Developmental Research Laboratories, Dainippon Pharmaceutical Co., Ltd.;Department of Pharmacology I, Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd.;Department of R&D Group of Biocybernetics, Dainippon Pharmaceutical Co., Ltd.

关键词: Mosapride citrate;    5-HT4 receptor agonist;    Conscious guinea pig;    Colonic Motility;    Receptor autoradiography;   

DOI  :  10.1254/jjp.90.313

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(26)Cited-By(22)It is known that 5-HT4 receptors in the colon of guinea pigs show a distribution similar to that in humans. Thus, we examined the effects of mosapride citrate (mosapride) and cisapride, two 5-HT4-receptor agonists, on colonic motility in conscious guinea pigs implanted with force transducers. Mosapride and cisapride administered intragastrically at doses of 3 – 30 mg/kg significantly enhanced the colonic motility. The enhancing effect of mosapride was antagonized by atropine or GR113808, a 5-HT4-receptor antagonist, but not by methysergide, a 5-HT1- and 5-HT2-receptor antagonist; ondansetron, a 5-HT3-receptor antagonist; or CP-99994, a tachykinin NK1-receptor antagonist. In vitro receptor autoradiography showed that mosapride and cisapride inhibit the specific binding of [125I]-SB207710, a selective radioligand of 5-HT4 receptors, in the colon of guinea pigs. These results suggest that mosapride enhances colonic motility through the 5-HT4-receptor activation in guinea pigs and may be useful for treating constipation in patients with colonic motility dysfunction.

【 授权许可】

Unknown