A cocaine hydrolase engineered from human butyrylcholinesterase selectively blocks cocaine toxicity and reinstatement of drug seeking in rats
A cocaine hydrolase engineered from human butyrylcholinesterase selectively blocks cocaine toxicity and reinstatement of drug seeking in rats
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DOI：
10.1038/sj.npp.1301666
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发表时间：
2008-10-01
影响因子：
7.6
通讯作者：
Carroll, Marilyn E.
中科院分区：
文献类型：
--
作者：
Brimijoin, Stephen;Gao, Yang;Carroll, Marilyn E.
人丁基胆碱酯酶（BChE）的连续合理突变与人血清白蛋白融合产生了一种有效的水解酶，为治疗可卡因过量和滥用提供了现实的选择。这种白蛋白- bche可以防止大鼠在注射通常致命的可卡因（100mg /kg, i.p）后癫痫发作，即使在给药后也能降低脑可卡因水平，并在抽搐开始后提供抢救。此外，它还选择性地阻断了先前自我服用可卡因的大鼠因可卡因而重新寻求药物的行为。酶治疗耐受性良好，可能值得探索在人类的临床应用。
Successive rational mutations of human butyrylcholinesterase (BChE) followed by fusion to human serum albumin have yielded an efficient hydrolase that offers realistic options for therapy of cocaine overdose and abuse. This albumin-BChE prevented seizures in rats given a normally lethal cocaine injection (100 mg/kg, i.p.), lowered brain cocaine levels even when administered after the drug, and provided rescue after convulsions commenced. Moreover, it selectively blocked cocaine-induced reinstatement of drug seeking in rats that had previously self-administered cocaine. The enzyme treatment was well tolerated and may be worth exploring for clinical application in humans.