Tasker R A, Nakatsu K
Can J Physiol Pharmacol. 1986 Sep;64(9):1160-3. doi: 10.1139/y86-197.
In previous studies from this laboratory it was found that dibutanoylmorphine (DBM) was more potent than morphine as an analgesic in rats and that it was less active than acetyl esters of morphine on behaviour. As DBM is a morphine prodrug, the aim of this work was to determine if rat brain homogenates were capable of deacylating DBM and monobutanoylmorphine (MBM) and to determine relative proportions of parent drug to metabolites in the brain in vivo. In 10% (w/v) brain homogenates, DBM was eliminated with a half-life of about 70 min (corrected for dilution), while MBM was eliminated 10 times as quickly. DBM and its metabolites were found in both blood and brain as early as 1 min after i.v. administration of DBM. After 5 min, the predominant form in blood was MBM and in brain it was DBM. Thus, rat brain possesses the capacity to metabolize DBM by deesterification and the parent drug, MBM, and morphine were found in blood and brain in vivo.
在本实验室之前的研究中发现，二丁酰吗啡（DBM）在大鼠中作为镇痛药比吗啡更有效，且在行为方面其活性低于吗啡的乙酰酯。由于DBM是一种吗啡前体药物，这项工作的目的是确定大鼠脑匀浆是否能够使DBM和单丁酰吗啡（MBM）脱酰基，并确定体内脑中母体药物与代谢物的相对比例。在10%（w/v）的脑匀浆中，DBM的消除半衰期约为70分钟（校正稀释后），而MBM的消除速度快10倍。静脉注射DBM后1分钟，在血液和脑中均发现了DBM及其代谢物。5分钟后，血液中的主要形式是MBM，而脑中是DBM。因此，大鼠脑具有通过脱酯作用代谢DBM的能力，且在体内血液和脑中发现了母体药物、MBM和吗啡。
