Ozaki A, Yoshidomi M, Sukamoto T
Pharmaceuticals R&D Center, Kanebo, Ltd., Osaka, Japan.
Jpn J Pharmacol. 1999 May;80(1):93-6. doi: 10.1254/jjp.80.93.
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.
研究了5-羟色胺3（5-HT3）受体拮抗剂KB-R6933（6-氨基-5-氯-1-异丙基-2-（4-甲基-1-哌嗪基）-苯并咪唑二马来酸盐）对实验性腹泻以及霍乱毒素刺激引起的肠液分泌的影响，并与雷莫司琼和洛哌丁胺进行了比较。在小鼠中，KB-R6933和雷莫司琼（0.03-1mg/kg，口服）可抑制5-羟色胺引起的腹泻，但对蓖麻油或前列腺素E2（PGE2）引起的腹泻无抑制作用。洛哌丁胺可显著抑制5-羟色胺、蓖麻油和PGE2引起的腹泻。所有受试药物均能抑制大鼠束缚应激引起的腹泻以及霍乱毒素刺激引起的肠液分泌。结果提示KB-R6933在治疗腹泻方面可能具有临床疗效。
