Carmona G N, Schindler C W, Shoaib M, Jufer R, Cone E J, Goldberg S R, Greig N H, Yu Q S, Gorelick D A
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
Exp Clin Psychopharmacol. 1998 Aug;6(3):274-9. doi: 10.1037//1064-1297.6.3.274.
A primary enzyme for the metabolism of cocaine is butyrylcholinesterase (BChE). To determine whether the systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect, rats were tested in a locomotor activity chamber after receiving 17 mg of cocaine per kg intraperitoneally. In rats pretreated intravenously with 5,000 IU of horse serum-derived BChE, the locomotor activity effect was significantly attenuated. BChE pretreatment increased plasma BChE levels approximately 400-fold. When added to rat plasma, this amount of BChE reduced the cocaine half-life from over 5 hr to less than 5 min. BChE altered the cocaine metabolic pattern such that the relatively nontoxic metabolite ecgonine methyl ester was produced, rather than benzoylecgonine. These results suggest that systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect of cocaine and thus should be investigated as a potential treatment for cocaine abuse.
可卡因代谢的一种主要酶是丁酰胆碱酯酶（BChE）。为了确定全身性给予BChE是否能充分增加可卡因的代谢以改变其行为效应，在大鼠腹腔注射每千克17毫克可卡因后，在运动活动箱中对其进行测试。在用5000国际单位马血清来源的BChE静脉预处理的大鼠中，运动活动效应显著减弱。BChE预处理使血浆BChE水平提高了约400倍。当添加到大鼠血浆中时，这种量的BChE将可卡因的半衰期从超过5小时缩短至不到5分钟。BChE改变了可卡因的代谢模式，从而产生了相对无毒的代谢物芽子碱甲酯，而不是苯甲酰芽子碱。这些结果表明，全身性给予BChE可以充分增加可卡因的代谢以改变可卡因的行为效应，因此应作为可卡因滥用的潜在治疗方法进行研究。
