[Pharmacological effects of the gastroprokinetic agent mosapride citrate].
Mosapride citrate (mosapride) is a novel gastroprokinetic agent that enhances the gastrointestinal motility by stimulating the 5-hydroxytryptamine4 (5-HT4) receptor. Mosapride dose-dependently enhanced the gastric emptying of a liquid or solid meal in rats with a potency equal to that of cisapride and more potent than that of metoclopramide. In rats, mosapride improved the gastric emptying delayed by gastroduodenal surgical intervention. In the conscious dogs with force transducers implanted chronically, mosapride stimulated antral and duodenal motility with a potency equal to those of cisapride. In isolated guinea-pig ileal longitudinal muscle preparations, mosapride enhanced the electrically stimulated contractions, and the enhancing effect of mosapride was antagonized by a high dose of tropisetron, a 5-HT4-receptor antagonist. In addition, mosapride inhibited [3H]-GR-113808 binding to 5-HT4 receptor sites of guinea-pig ileum and striatum. Mosapride had no affinity for dopamine D2 receptor, whereas metoclopramide and cisapride had a high affinity for dopamine D2 receptor. In isolated guinea-pig papillary muscles, mosapride did not prolong the duration of action potentials, whereas cisapride concentration-relatedly prolonged it. In conclusion, mosapride is a selective and potent 5-HT4 receptor agonist and improves gastrointestinal symptoms in patients with non-ulcer dyspepsia without causing the extrapyraminal syndrome associated with dopamine-D2-receptor blockage and adverse cardiovascular effects such as torsadoes de points.
Yoshida
N
N
Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D004285:Dogs; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009025:Morpholines / Q000494:pharmacology*; D051381:Rats
D001549:Benzamides; D005765:Gastrointestinal Agents; D009025:Morpholines; C062720:mosapride