Akio Ozaki, Mikio Yoshidomi and Takayuki Sukamoto
Pharmaceuticals R&D Center, Kanebo, Ltd., 1-5-90, Tomobuchi-cho,
Miyakojima-ku, Osaka 534-8666, Japan
Abstract: The effects of a 5-hydroxytryptamine3 (5-HT3)-receptor
antagonist KB-R6933 (6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl)-benzimidazole
dimaleate) on experimental diarrhea and on intestinal fluid secretion stimulated
by cholera toxin were examined and compared with those of ramosetron and
loperamide. KB-R6933 and ramosetron (0.03 - 1 mg/kg, p.o.) inhibited the
diarrhea induced by 5-HT, but not that by castor oil or prostaglandin E2
(PGE2), in mice. Loperamide significantly inhibited the diarrhea
induced by 5-HT, castor oil and PGE2. All drugs tested inhibited
the diarrhea induced by restraint stress and the intestinal fluid secretion
stimulated by cholera toxin in rats. The results suggest the possibility
that KB-R6933 may have clinical efficacy in the treatment of diarrhea.
Keywords: KB-R6933, 5-HT3 receptor antagonist, Diarrhea