| Project/Area Number |
59870084
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Faculty of Pharmaceutical Sciences University of Tokyo |
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Principal Investigator |
HIROBE Masaaki Faculty of Pharmaceutical Sciences, University of Tokyo Professor, 薬学部, 教授 (20012594)
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| Co-Investigator(Kenkyū-buntansha) |
TANI Hideo Tokyo Research Laboratories, Kowa Co., Ltd., 東京研究所, 所長
TAKAYANAGI Issei Toho University School of Pharmaceutical Sciences Professor, 薬学部, 教授 (70012599)
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1986: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1985: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1984: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | normorphine / norcodeine / N-allylnormorphine / N-allylnorcodeine / N-アリルモルヒネ / N-アリルノルコデイン / エポキシド / 含フッ素コデイン-7、8-オキサイド |
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| Research Abstract |
The narcotic analgesic are employed primarily for the relief of pain, but their use entails the risk of producing physical and sometimes psycological dependence. There are as yet no agents effective against severe pain that are entirely free of the risk. Recently, our group has synthesized 7,8-epoxide of morphine. This compound has almost same analgesic activity compared with morphine, and much less dependence liability.
Our Project is to confirm the structure-activity relationship of 7,8-epoxide of narcotic drugs and to separate the pharmacological activity and the adverse reaction ( dependency, tolerance, etc. ). 1. Synthesis
7,8-epoxides of normorphine, norcodeine, N-allylnormorphine and N-allyl-norcodeine were synthesized. They have good enough stability to investigate their pharmacological activity.
2. Pharmacological activity
The analgesic activity of these 7,8-epoxides was determined by the method of pressure stimuli on the rat tail. All the tested compounds dose-dependently exhibited their activity. Further it was found that the introduction of 7,8-epoxy moiety into morphine skeleton trends toward some decrease in dependency liability and in the development of tolerance, and N-ally17,8-epoxides have more pure narcotic antagonistic action than the parent compounds have.
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