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Here, I briefly review studies on an active metabolite of morphine and characterization of enzymes responsible for the formation of the glucuronide in our laboratory. Morphine has been used extensively in pain clinic and was found biotransformed mainly by glucuronidation to a major inactive glucuronide; morphine-3-glucuronide (M-3-G) and also to a minor active metabolite; morphine-6-glucuronide (M-6-G). The very potent metabolite has been attracted much interest in a role of morphine analgesia in humans. The pharmacokinetic results are now interpreted as demonstrating that the active glucuronide had a positive effect on the analgesia. Recently, researchers have disclosed the presence of an unique opioid receptor for the glucuronide. Our recent experimental evidence from expression of two cDNA clones of glucuronidating enzymes from guinea pig liver supported the view that the enzymes form hetero-oligomers by accessing a broader range of compounds as in the active metabolite than homo-oligomers. A natural follow-up to the present evidence would be to carry out for the genomic information in regulatory molymorphism in drug metabolism by glucuronidation.

An Active Metabolite ofMorphine and the Responsible Glucuronosyltransferase for its Formation.