Lipkowski A W, Carr D B, Langlade A, Osgood P F, Szyfelbein S K
Department of Anesthesia, Massachusetts General Hospital, Boston 02114.
Life Sci. 1994;55(2):149-54. doi: 10.1016/0024-3205(94)90106-6.
To assess whether stoichiometric manipulation of morphine (M) metabolism can enhance analgesia or slow the development of M tolerance we co-administered M-3- glucuronide (M3G) during single or repeated doses of morphine in rats. Although M3G itself lacked analgesic activity, co-injection of M3G with M increased and prolonged analgesia beyond that seen with M. In addition, diminution of the acute analgesic effect of M after 3 once-daily doses of M did not occur after daily co-injection of M3G and M. Thus the traditional view that tolerance to the effects of M is due solely to effects mediated through opioid receptors must be broadened to include the contributions of enzyme induction or stoichiometric equilibration of M3G in this process.
为了评估对吗啡（M）代谢进行化学计量操纵是否能增强镇痛效果或减缓M耐受性的发展，我们在大鼠单次或重复给予吗啡的过程中共同给予了M - 3 - 葡萄糖醛酸苷（M3G）。尽管M3G本身缺乏镇痛活性，但将M3G与M共同注射可增强并延长镇痛效果，超过单独使用M时所见的效果。此外，在每日共同注射M3G和M后，连续3次每日注射M后M的急性镇痛效果并未减弱。因此，传统观点认为对M作用的耐受性仅归因于通过阿片受体介导的效应，必须加以扩展，以纳入该过程中酶诱导或M3G化学计量平衡的作用。
