Dean R A, Harper E T, Dumaual N, Stoeckel D A, Bosron W F
Department of Pathology, Indiana University School of Medicine, Indianapolis 46202-5200.
Toxicol Appl Pharmacol. 1992 Nov;117(1):1-8. doi: 10.1016/0041-008x(92)90210-j.
The coabuse of cocaine and ethanol occurs with high frequency and increases the risk of cocaine-related morbidity and mortality. The mechanisms mediating the toxic interactions of cocaine and ethanol are not clearly defined. This study examined the effects of acute ethanol administration on the metabolism of cocaine in the male Wistar rat. Intraperitoneal administration of 2 g/kg ethanol 30 min prior to administration of 25 mg/kg cocaine resulted in the formation of two ethylated derivatives of cocaine, benzoylecgonine ethyl ester (cocaethylene) and benzoylnorecgonine ethyl ester (norcocaethylene) in liver, brain, and serum. Fifteen minutes after cocaine administration, the tissue levels of cocaethylene were 22, 10, and 9% of the cocaine recovered from liver, serum, and brain, respectively. Ethanol pretreatment increased cocaine concentrations in liver and benzoylnorecgonine concentrations in liver and serum. The increased morbidity and hepatotoxicity seen with acute combined administration of cocaine and ethanol may be due to the formation of the toxic ethylated and N-demethylated metabolites of cocaine. Ethanol pretreatment decreased benzoylecgonine concentrations in serum and liver. The most important consequence of ethanol-induced inhibition of the normally rapid hydrolysis of cocaine to benzoylecgonine may be a decrease in benzoylecgonine-mediated vasoconstriction.
可卡因和乙醇的共同滥用情况频繁发生，会增加与可卡因相关的发病和死亡风险。介导可卡因和乙醇毒性相互作用的机制尚未明确界定。本研究检测了急性给予乙醇对雄性Wistar大鼠体内可卡因代谢的影响。在给予25mg/kg可卡因前30分钟腹腔注射2g/kg乙醇，结果在肝脏、大脑和血清中形成了可卡因的两种乙基化衍生物，即苯甲酰爱康宁乙酯（可口卡因）和苯甲酰去甲爱康宁乙酯（去甲可口卡因）。给予可卡因15分钟后，可口卡因的组织水平分别为从肝脏、血清和大脑中回收的可卡因的22%、10%和9%。乙醇预处理增加了肝脏中的可卡因浓度以及肝脏和血清中的苯甲酰去甲爱康宁浓度。急性联合给予可卡因和乙醇时出现的发病率增加和肝毒性可能归因于可卡因毒性乙基化和N-去甲基化代谢物的形成。乙醇预处理降低了血清和肝脏中的苯甲酰爱康宁浓度。乙醇诱导的对可卡因正常快速水解为苯甲酰爱康宁的抑制作用最重要的后果可能是苯甲酰爱康宁介导的血管收缩作用减弱。
