[Our drug metabolism studies during the last four decades]

The drug metabolism studies in which we have been engaging for about 40 years since 1952 are briefly reviewed in this paper. Our main efforts were initially made to elucidate the metabolic fates of various abused drugs including barbiturates, carbamates, opioids, amphetamines and cannabinoids in mammals from pharmacological and toxicological points of view. Among the interesting findings obtained from these studies, the most remarkable one was that morphine-6-glucuronide, a minor metabolite of morphine, has much stronger analgesic activity than morphine. Recently we have also been interested in clarifying the enzyme system involved in the metabolic pathways of the above drugs. Several cytochrome P-450 isozymes were thus purified from the liver microsomes of mammals and their role in oxygenation of amphetamines and cannabinoids were elucidated. The finding that MALDO (microsomal aldehyde oxygenase), a purified P-450 isozyme, could catalyze an oxidation of lipid-soluble aldehydes to the corresponding carboxylic acids was most noticeable. Metabolic and toxicologic studies on furylfuramide (AF-2) and polychlorinated biphenyl (PCB) have also been performed using rats and other animal species, and some interesting results were obtained.