Antiallergic Effect of ZCR-2060: Antihistaminic Action.
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概要
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The antihistaminic effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060), a newly synthesized antiallergic agent, was investigated in both in vitro and in vivo studies. ZCR-2060 clearly antagonized histamine-induced contraction of isolated guinea pig ileum and trachea. In contrast, carbachol-, BaCl<SUB>2</SUB> and 5-hydroxytryptamine-induced contractions of isolated guinea pig ileum were slightly inhibited by higher concentrations of ZCR-2060. <SUP>3</SUP>H-Mepyramine specific binding to membranes from guinea pig lung and brain were markedly inhibited by ZCR-2060 in a concentration-dependent fashion. In the in vitro studies, the antihistaminic effect of ZCR-2060 was greater than those of cetirizine and terfenadine, but was less than that of ketotifen. In the in vivo studies, ZCR-2060 significantly inhibited the histamine-induced cutaneous reaction in rats, when administered orally 1 hr before the histamine injection. Moreover, ZCR-2060 has a long-lasting antihistaminic effect. In the in vivo studies, the antihistaminic effect of ZCR-2060 was found to be greater than that of cetirizine and terfenadine, and it was the same as that of ketotifen. Thiopental-induced sleep and spontaneous ambulatory activity in mice, however, were unaffected by ZCR-2060 at higher doses. These results indicate that ZCR-2060 has a potent, selective and long acting histamine H<SUB>1</SUB>-receptor antagonistic action without causing any unwanted CNS side effect.
- 公益社団法人 日本薬理学会の論文
著者
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Omata Takeshi
Department Of Applied Research Central Laboratories Zeria Pharmaceutical Co. Ltd.
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Segawa Yoshihide
Department Of Pharmacology Central Research Laboratories Zeria Pharmaceutical Co. Ltd.
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Matsuda Kazuo
Department Of Agricultural Biochemistry Faculty Of Agriculture Tohoku University
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Ikeda Yugo
Department Of Pharmacology Central Research Laboratories Chugai Pharmaceutical Co. Ltd.
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Nagai Hiroichi
Department Of Applied Pharmacology Graduate School Of Medicine And Pharmaceutical Sciences University Of Toyama
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Yoshida Kenji
Department of Biochemistry, Kinki University School of Medicine
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Segawa Yoshihide
Department of Pharmacology, Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.
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Abe Tooru
Department of Pharmacology, Gifu Pharmaceutical University
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Matsumura Toshihiro
Department of Pharmacology, Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.
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