Effect of the 5-hydroxytryptamine(3) (5-HT3)-receptor antagonist KB-R6933 on experimental diarrhea models

The effects of a 5-hydroxytryptamine(3) (5-HT3)-receptor antagonist KB-R693 3 (6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl)-benzimidazole di maleate) on experimental diarrhea and on intestinal fluid secretion stimula ted by cholera toxin were examined and compared with those of ramosetron an d loperamide. KB-R6933 and ramosetron (0.03 -1 mg/kg, p.o.) inhibited the d iarrhea induced by 5-HT, but not that by castor oil or prostaglandin E-2 (P GE(2)), in mice. Loperamide significantly inhibited the diarrhea induced by 5-HT, castor oil and PGE(2). All drugs tested inhibited the diarrhea induc ed by restraint stress and the intestinal fluid secretion stimulated by cho lera toxin in rats. The results suggest the possibility that KB-R6933 may h ave clinical efficacy in the treatment of diarrhea.