Chan A W, Schanley D L, Langan M C, Leong F W, Penetrante M L
Research Institute on Alcoholism, New York State Division of Alcoholism and Alcohol Abuse, Buffalo 14203.
Pharmacol Biochem Behav. 1990 Feb;35(2):363-6. doi: 10.1016/0091-3057(90)90170-m.
Although chronic ethanol administration in C57BL/6J mice did not cause an induction of ethanol metabolism, it altered the metabolism of chlordiazepoxide (CDP). Significantly lower blood levels of CDP, but higher levels of N-desmethyl CDP (NDCDP), were observed in ethanol-dependent mice compared to pair-fed controls during the first hour after CDP injection. Mice treated chronically with CDP showed significantly lower blood levels of CDP and NDCDP than pair-fed controls after a test dose of CDP. In response to an injection of ethanol, the CDP-dependent mice had lower blood alcohol levels (BAL) than the pair-fed controls, but the rate of fall of BAL was not different in the two groups. Thus, chronic CDP treatment affected the absorption and distribution of ethanol. These results provide a metabolic basis for the manifestations of CDP tolerance and ethanol cross-tolerance that have been reported in CDP-dependent mice.
虽然在C57BL/6J小鼠中慢性给予乙醇不会引起乙醇代谢的诱导，但它改变了氯氮卓（CDP）的代谢。在注射CDP后的第一个小时内，与配对喂食的对照组相比，乙醇依赖小鼠的CDP血药浓度显著降低，但N-去甲基氯氮卓（NDCDP）的水平更高。长期用CDP治疗的小鼠在给予一次测试剂量的CDP后，其CDP和NDCDP的血药浓度比配对喂食的对照组显著降低。对注射乙醇的反应，CDP依赖小鼠的血液酒精浓度（BAL）低于配对喂食的对照组，但两组BAL的下降速率没有差异。因此，长期的CDP治疗影响了乙醇的吸收和分布。这些结果为CDP依赖小鼠中已报道的CDP耐受性和乙醇交叉耐受性的表现提供了代谢基础。
