Characteristic glucuronidation pattern of physiologic concentration of morphine in rat brain

Formation of conjugated metabolites from morphine at a very low level in br ain was studied in vitro in rats. Incubation of a low concentration of H-3- morphine with brain homogenate followed by two successive high-performance liquid chromatographic analyses showed that endogenous morphine is converte d by brain enzymes to its 3- and 6-glucuronides (M-3-G and M-6-G), and code ine glucuronide (Cod-G). However, the formation of morphine-6-sulfate was l ikely to be low if it was produced at all. All of the cerebral hemisphere, brain stem and cerebellum were capable of producing M-3-G, M-6-G and Cod-G, although there were differences in selectivity. The capacity of the brain for glucuronide formation was far less than that of the liver, but UDP-gluc uronosyltransferase in brain was much more selective in forming M-6-G and C od-G than liver enzymes. (C) 2000 Elsevier Science Inc. All rights reserved .