Amino Acids and Peptides. XXIV. Preparation and Antinociceptive Effect of [D-Ala^2,(N-Me)Phe^4]Enkephalin Analog-Poly(Ethylene Glycol)Hybrids
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概要
- 論文の詳細を見る
Hybrids of amino-poly(ethylene glycol) (a PEG) and [D-Ala^2,(N-Me)Phe^4]enkephalin analogs, H-Tyr-D-Ala-Gly-(Me)Phe-aPEG, H-Tyr-D-Ala-Gly-(Me)Phe-Leu-aPEG and H-Tyr-D-Ala-Gly-(Me)Phe-D-Leu-aPEG, were prepared by the solution method and their antinociceptive properties were examined in comparison with those of the peptides. H-Tyr-D-Ala-Gly-(Me)Phe-OH and H-Tyr-D-Ala-Gly-(Me)Phe-Leu-OH themselves at intracerebroventricular (i.c.v.) doses of 10-30nmol/animal produced an antinociceptive effect which was less potent than that of i.c.v. morphine, 3μg/animal, and H-Tyr-D-Ala-Gly-(Me)Phe-D-Leu-OH did not have any marked effect. However, the antinociceptive effects of H-Tyr-D-Ala-Gly-(Me)Phe-Leu-OH and H-Tyr-D-Ale-Gly-(Me)Phe-D-Leu-OH were remarkably potentiated by hybrid formation with aPEG to levels higher than that of 3μg/mouse of morphine, and the effect lasted at least 120min. In contrast, the effect of H-Tyr-D-Ala-Gly-(Me)Phe-OH was rather diminished by hybrid formation. In view of the low toxicity and weak immunogeic properties of aPEG, the hybrids could be useful in therapy of patients for relieving chronic and severe pain.
- 社団法人日本薬学会の論文
- 1994-09-15
著者
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川崎 紘一
Faculty of Pharmaceutical Sciences, Kobe Gakuin University
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前田 光子
Faculty of Pharmaceutical Sciences, Kobe Gakuin University
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中尾 薫
長崎大学薬学部薬物学教室
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金戸 洋
長崎大学薬学部薬物学教室
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高橋 正克
Faculty of Pharmaceutical Sciences, Nagasaki University
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中尾 薫
Faculty of Pharmaceutical Sciences, Nagasaki University
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金戸 洋
Faculty of Pharmaceutical Sciences, Nagasaki University
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高橋 正克
長崎大学薬学部医療情報・分析学教室
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前田 光子
Life Science Center Faculty Of Pharmaceutical Sciences Kobe Gakuin University
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金戸 洋
Faculty Of Pharmaceutical Sciences Nagasaki University 1-14 Bunkyocho Nagasaki
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川崎 紘一
Life Science Center Faculty Of Pharmaceutical Sciences Kobe Gakuin University
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Maeda M
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Nagasaki University:faculty Of Pharmac
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Kawasaki Keiko
Biological Science Laboratories Kao Corporation
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川崎 紘一
Faculty Of Pharmaceutical Sciences & Cooperative Research Center Of Life Sciences Kobe Gakuin Un
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Maeda Masatomo
Laboratory Of Biochemistry And Molecular Biology Graduate School Of Pharmaceutical Sciences Osaka Un
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