Add time:09/02/2019         Source:sciencedirect.com

We examined the effect of ramosetron, a potent serotonin (5-HT)3-receptor antagonist for irritable bowel syndrome with diarrhea, on conditioned fear stress (CFS)-induced defecation and normal (non-stressed) defecation in rats and compared ramosetron with the antidiarrheal agent loperamide and the spasmolytic agents trimebutine and tiquizium. Ramosetron, loperamide, trimebutine, and tiquizium significantly inhibited CFS-induced defecation in a dose-dependent manner with ED50(95% confidence limit) values of 0.019 (0.01 –0.028), 9.4 (4.0 –22), 850 (520 –2,400), and 300 (190 –450) mg/kg, respectively. A significant effect of ramosetron on CFS-induced defecation appeared at 10 min after dosing and was sustained for 8 h. In contrast, loperamide, trimebutine, and tiquizium significantly inhibited CFS-induced defecation between 1 –8, 1 –4, and 1–8h after administration, respectively. High doses of ramosetron did not affect normal defecation, whereas loperamide, trimebutine, and tiquizium significantly inhibited this process. In conclusion, ramosetron has potent, rapid-onset, and long-lasting inhibitory effects on CFS-induced defecation in rats, but does not influence normal defecation. The present findings indicate that ramosetron will be a useful therapeutic agent for irritable bowel syndrome with diarrhea, showing greater efficacy and safety than other antidiarrheal and spasmolytic agents.

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