DISCOVERY OF A STRUCTURALLY NOVEL OPIOID K-AGONIST DERIVED FROM 4,5-EPOXYMORPHINAN
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概要
- 論文の詳細を見る
A new type of K-agonist, 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan hydrochloride (1,TRK-820), was discoverd by a new working hypothesis. The "message-address concept" for opioid antagonists and the "accessory site" for general antagonists were applied to design TRK-820. A unique structural feature of TRK-820,which is different from other prototypical K-opioid receptor agonists, is the existence of the 4,5-epoxymorphinan structure with a tyrosine-glysine moiety for endogenous opioid peptides such as dynorphins. TRK-820 exhibited high potency and high K-selectivity in guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. In the mouse acetic-acid-induced writhing model and mouse tail flick model of antinociception, TRK-820 was 85-140 times more potent than morphine and 85-350 times more potent than U-50488H. This structurally novel K-agonist showed neither aversion nor preference in the Conditioned Place Preference test, in spite of the fact that prototypes of K-agonists (U-50488H derivatives) demonstrated aversion.
- 公益社団法人日本薬学会の論文
- 1998-02-15
著者
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Nagase H
Basic Research Laboratories Toray Industries Inc.
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Nagase Hiroshi
Pharmaceutical Research Laboratories Toray Industries Inc.
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Endo T
Graduate School Of Pharmaceutical Sciences Hokkaido University
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Kawai K
Hoshi Univ. Tokyo Jpn
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Kawai Kouji
Department Of Urology Institute Of Clinical Medicine University Of Tsukuba
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Kawai Kouji
Department Of Biochemistry Meikai University School Of Dentistry
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Hayakawa Jun
Departments Of Pediatrics And Biochemistry And Molecular Biology Nippon Medical School
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Hayakawa Jun
Hitachi Ltd. Central Research Laboratory
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Hayakawa Jun
Pharmaceutical Research Laboratories Toray Industries Inc.
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Hayakawa Jun
Department Of Anesthesia Kanagawa Cancer Center Hospital
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ENDO TAKASHI
Department of Surgery, Saitama Municipal Hospital
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Kawai Koji
Basic Research Laboratories Toray Industries Inc.
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TAJIMA Chiko
Basic Research Laboratories, Toray Industries, Inc.
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TAKEZAWA Yuko
Basic Research Laboratories, Toray Industries, Inc.
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NAGASE Hiroshi
Department of Medicinal Chemistry, Basic Research Laboratory, Toray Industries, Inc.,
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KAWAMURA Kuniaki
Department of Medicinal Chemistry, Basic Research Laboratory, Toray Industries, Inc.,
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TAKEZAWA Yuko
Department of 2nd Pharmacology, Basic Research Laboratory, Toray Industries, Inc.,
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MATSUURA Hirotoshi
Department of 2nd Pharmacology, Basic Research Laboratory, Toray Industries, Inc.,
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TAJIMA Chiko
Department of 2nd Pharmacology, Basic Research Laboratory, Toray Industries, Inc.,
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Takezawa Yuko
Basic Research Laboratories Toray Industries Inc.
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Endo T
Tsukuba Research Center Of The Real World Computing Partnership (rwcp)
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Tajima Chiko
Basic Research Laboratories Toray Industries Inc.
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Matsuura H
Healthcare Research Institute Wakunaga Pharmaceutical Co. Ltd.
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Nagase Hiroshi
Department Of Information And Computer Engineering
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Endo Takashi
Department Of Surgery Keio University School Of Medicine
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Endo Takashi
Department Of Radiology Kitasato University School Of Medicine
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Endo Takashi
Department Of Applied Chemistry Tokai University
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