Synthesis and Pharmacological Activity of Morphine Epoxide Derivatives.

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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. Synthesis7,8-epoxides of normorphine, norcodeine, N-allylnormorphine and N-allyl-norcodeine were synthesized. They have good enough stability to investigate their pharmacological activity.2. Pharmacological activityThe 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.