title: Morphine metabolism revisited: I. Metabolic activation of morphine to a reactive species in rats.
abstract: Treatment of fasted rats with relatively high doses of morphine rapidly results in depletion of hepatic glutathione (GSH) content and marked elevation of serum transaminase activity. Such morphine-induced response has been generally attributed to central nervous system mediated effects of the drug. We now report that this response might be due to a direct effect of the drug in the liver. That is, its metabolic activation to reactive electrophilic metabolite(s), by the hepatic cytochrome P-450-dependent mixed function oxidase system. Structure-activity relationships of morphine and its congeners indicate that the (-)-3-hydroxy-N- methylmorphinan moiety is linked with the potential of these opioids to deplete hepatic GSH and to raise serum transaminases in rats.
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004090:Dihydromorphine / Q000378:metabolism; D004790:Enzyme Induction; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D009020:Morphine / Q000378:metabolism* / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism; D017450:Receptors, Opioid, mu
chemical_list: D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C028485:dihydromorphine receptor; D008748:Methylcholanthrene; D009020:Morphine; D003577:Cytochrome P-450 Enzyme System; D004090:Dihydromorphine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D010634:Phenobarbital