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薬理と治療
Abstract
Ramosetron, a potent and selective serotonin(5−HT)3 receptor antagonist, is known to possess therapeutic effects on various symptoms in patients suffered from irritable bowel syndrome(IBS)with diarrhea, as well as inhibitory effects on stress−induced abnormal defecation and colonic hyperalgesia in animals. Although existing drugs such as anti−diarrheal agents, spasmolytics, and synthetic polymer, are widely prescribed for IBS patients in present, no study has yet been carried out on the effects of co−administration of ramosetron with such drugs. In the present study, therefore, we examined the effects on ramosetron, polycarbophil, a synthetic polymer, and their concomitant administration on restraint stressand 5−HT−induced diarrhea in rats and mice. Diarrhea was induced by restraint stress for 3 h in rats that had been fasted overnight, or intraperitoneal administration with 5−HT at a dose of 3 mg/kg in mice. Oral administration of ramosetron and polycarbophil inhibited restraint stress− and 5−HT−induced diarrhea in a dose−dependent manner. Co−administration of ramosetron with polycarbophil showed significant synergistic effects in both diarrheal models. These results indicate a possibility that co−administration of ramosetron with polycarbophil possesses useful synergistic effects in clinical practice.(Jpn Pharmacol Ther 2008;36:805−10)KEY WORDS Ramosetron, Polycarbophil, Diarrhea, Co−administration
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