Comparison of the Antidiarrheal Effects of Zaldaride Maleate and Its Optical Isomers in Rats
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概要
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Zaldaride maleate (ZAL), a calmodulin inhibitor, that ameliorates secretory diarrhea in rodents, has a racemic structure. In this study, we compared the antidiarrheal and antisecretory effects of ZAL and its optical isomers, R(-)-isomer and S(+)-simer, in rats. In Ussing chamber experiments, the inhibitory action of ZAL on acetylcholine-induced ion transport in the rat colonic mucosa was equipotent for both optical isomers, with IC_<50> values of apprpximately 3-4 μmol/l. In castor-oil-induced diarrhea, ZAL and its S(+)-isomer inhibited the incidence of diarrhea, whereas the R(-)-isomer had no effect. In 16,16-dimethyl prostaglandin E_2-induced diarrhea, ZAL, the S(+)-isomer and the R(-)-isomer significantly ameliorated diarrhea at doses of 30,10 and 30 mg./kg (p.o.), respectively; the ED_<50> values were 25,10 and above 30 mg/kg (p.o.), respectively. The pharmacokinetic parameters after administration of 30 mg/kg (p.o.) of each compound were as follows : ZAL (C_<max> : 378 ng/ml, AUC_<0-12> : 1650 ng-h/ml); S(+)-isomer (C_<max> : 565 ng/ml, AUC_<0-12> : 2230 ng-h/ml) and R(-)-isomer (C_<max> : 271 ng/ml, AUC_<0-12> : 613 ng-h/ml) (mean, N=4). In conclusion, despite the fact that the antisecretory actions of ZAL and its optical isomers are the same, the antidiarrheal actions of ZAL and its S(+)-isomer are more potent than that of the R(-)-isomer. The antidiarrheal actions of ZAL and its optical isomers may be related to plasma levels.
- 社団法人日本薬学会の論文
- 2000-04-01
著者
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OHMORI Kenji
Department of Crystalline Materials Science, Graduate School of Engineering, Nagoya University
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Ohmori K
Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd.
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OHMORI Kenji
Drug Development Research Laboratories, Pharmaceutical Research, Institute, Kyowa Hakko Kogyo Co., L
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Ohmori K
Kyowa Hakko Kogyo Co. Ltd. Shizuoka Jpn
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Ohmori Kenji
Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd.
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Ohmori Kenji
Department Of Crystalline Materials Science Graduate School Of Engineering Nagoya University
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HORIKOSHI Kaori
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Kogyo Co., Ltd.
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AIKAWA Nobuo
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Lt
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Aikawa N
Kyowa Hakko Kogyo Co. Ltd. Shizuoka Jpn
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Aikawa Nobuo
Drug Development Research Laboratories Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd.
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MAEDA Hiroshi
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Lt
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KOBAYASHI Hiroyuki
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Lt
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Ohmori K
Drug Development Research Laboratories Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd
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Ohmori Kenji
Drug Development Research Laboratories Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd.
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Horikoshi Kaori
Drug Development Research Laboratories Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd.
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Kobayashi H
Department Of Earth & Spece Science Graduate School Of Science Osaka University
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Kobayashi H
Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd.
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Horikoshi Kaori
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
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