Effect of ramosetron on conditioned emotional stress-induced colonic dysfunction as a model of irritable bowel syndrome in rats

The aim of this study was to establish a pathophysiologic model of irritable bowel syndrome, and then to evaluate the pharmaceutical efficacy of ramosetron, a potent serotonin 3 (5-HT 3) receptor antagonist, and other anti-irritable bowel syndrome agents in this model. Rats stressed by a conditioned...

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Veröffentlicht in:European journal of pharmacology 2007-11, Vol.573 (1), p.190-195
Hauptverfasser: Funatsu, Toshiyuki, Takeuchi, Asako, Hirata, Takuya, Keto, Yoshihiro, Akuzawa, Shinobu, Sasamata, Masao
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Sprache:eng
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Zusammenfassung:The aim of this study was to establish a pathophysiologic model of irritable bowel syndrome, and then to evaluate the pharmaceutical efficacy of ramosetron, a potent serotonin 3 (5-HT 3) receptor antagonist, and other anti-irritable bowel syndrome agents in this model. Rats stressed by a conditioned stress procedure exhibited marked prolongation of freezing time, an index of fear level, and an increase in the frequency of defecation ( P < 0.01). A corticotropin-releasing factor (CRF) antagonist, α-helical CRF, inhibited both defecation and freezing behavior, while the antidiarrheal loperamide inhibited defecation only. The 5-HT 3 receptor antagonists ramosetron, cilansetron and alosetron also inhibited defecation (ED 50 values: 0.012, 0.094, 0.078 mg/kg p.o., respectively) without affecting freezing behavior. Ramosetron showed longer-lasting effect on defecation than cilansetron. Stress also resulted in increases in both proximal and distal colonic transit rates. Ramosetron and other 5-HT 3 receptor antagonists at doses inhibiting stress-induced defecation also ameliorated both stress-stimulated colonic transit rates. These results suggest that ramosetron, as well as agents used for the treatment of irritable bowel syndrome with diarrhea, has beneficial effects against emotional stress-induced colonic dysfunction. Furthermore, this emotional stress model may be useful in evaluation of drugs to treat irritable bowel syndrome presenting with diarrhea.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2007.06.041