Schechter M D, Meehan S M
Department of Pharmacology, Northeastern Ohio Universities, College of Medicine, Rootstown 44272, USA.
Pharmacol Biochem Behav. 1995 Sep;52(1):245-8. doi: 10.1016/0091-3057(95)00098-h.
The HS line of mice was used to determine the LD50 values for cocaine and ethanol, as well as for cocaethylene, the enzymatic product of their coadministration. The LD50 of cocaethylene was found to be significantly lower than that of cocaine, and both were more potent in their lethality than ethanol. When a low-lethality dose of cocaine was administered with a nonlethal dose of ethanol, the result was a significant increase in the prevalence of lethality. Thus, the lethal effects of the dose of cocaine used were increased by the dose of ethanol administered such that the two drugs in combination were equipotent to cocaethylene. The results are discussed in light of the ability of the liver, via transestification, to rapidly form cocaethylene from cocaine in addition to ethanol's ability to decrease the catabolism of cocaine. Thus, the possibility exists that the increased lethality observed is produced by both the production of the more lethal cocaethylene and sustained levels of cocaine.
采用HS品系小鼠来确定可卡因、乙醇以及它们共同给药时的酶促产物——古柯乙烯的半数致死量（LD50）值。发现古柯乙烯的LD50显著低于可卡因，并且二者在致死性方面都比乙醇更强。当给予低致死剂量的可卡因与非致死剂量的乙醇时，致死率显著增加。因此，所用可卡因剂量的致死效应因所给予的乙醇剂量而增强，使得这两种药物联合使用时与古柯乙烯具有同等效力。鉴于肝脏通过转酯化作用能够迅速从可卡因中生成古柯乙烯，以及乙醇能够降低可卡因的分解代谢能力，对这些结果进行了讨论。因此，观察到的致死率增加有可能是由更具致死性的古柯乙烯的产生以及可卡因的持续水平所致。
