Attenuation of cocaine-induced locomotor activity by butyrylcholinesterase.

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从而改变一种行为效应，大鼠在腹腔内接受每千克17毫克可卡因后，在活动箱中进行测试。在大鼠经静脉预先给予5000国际单位马血清来源的BChE后，活动效应显著减弱。BChE预处理使血浆BChE水平增加了约400倍。当加入到大鼠血浆中时，这种量的BChE使可卡因的半衰期从超过5小时减少到不到5分钟。BChE改变了可卡因的代谢模式，使得产生相对无毒的代谢产物爱康宁甲酯，而非苯甲酰爱康宁。这些结果表明，全身性给予BChE能够充分增加可卡因的代谢，从而改变可卡因的一种行为效应，因此应作为一种潜在的可卡因滥用治疗方法进行研究。