EFFECTS OF ETHANOL ON COCAINE METABOLISM - FORMATION OF COCAETHYLENE AND NORCOCAETHYLENE
EFFECTS OF ETHANOL ON COCAINE METABOLISM - FORMATION OF COCAETHYLENE AND NORCOCAETHYLENE
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DOI：
10.1016/0041-008x(92)90210-j
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发表时间：
1992-11-01
影响因子：
3.8
通讯作者：
BOSRON, WF
中科院分区：
文献类型：
--
作者：
DEAN, RA;HARPER, ET;BOSRON, WF
可卡因和乙醇同时滥用的发生频率很高，增加了与可卡因有关的发病率和死亡率的风险。介导可卡因和乙醇毒性相互作用的机制尚不清楚。本研究探讨了急性乙醇给药对雄性Wistar大鼠可卡因代谢的影响。在给予25 mg/kg可卡因之前30 min腹膜内给予2 g/kg乙醇导致在肝脏、脑和血清中形成可卡因的两种乙基化衍生物，苯甲酰芽子碱乙酯（cocaethylene）和苯甲酰去甲芽子碱乙酯（norcocaethylene）。可卡因给药后15分钟，可卡因的组织水平分别为从肝脏、血清和脑中回收的可卡因的22%、10%和9%。乙醇预处理增加肝脏中可卡因浓度和肝脏和血清中苯甲酰去甲肾上腺素浓度。可卡因和乙醇急性联合给药时观察到的发病率和肝毒性增加可能是由于可卡因毒性乙基化和N-脱甲基代谢产物的形成。乙醇预处理降低血清和肝脏中苯甲酰芽子碱的浓度。乙醇诱导的可卡因快速水解为苯甲酰芽子碱的抑制作用的最重要的结果可能是苯甲酰芽子碱介导的血管收缩减少。
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.