A cocaine hydrolase engineered from human butyrylcholinesterase selectively blocks cocaine toxicity and reinstatement of drug seeking in rats

被引：108

作者：

Brimijoin, Stephen ^{[1
]}

Gao, Yang ^{[1
]}

Anker, Justin J. ^{[2
]}

Gliddon, Luke A. ^{[2
]}

LaFleur, David ^{[3
]}

Shah, R. ^{[3
]}

Zhao, Qinghai ^{[3
]}

Singh, M. ^{[3
]}

Carroll, Marilyn E. ^{[2
]}

机构：

[1] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA

[2] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA

[3] CoGenesys Inc, Drug Dev, Rockville, MD USA

来源：

NEUROPSYCHOPHARMACOLOGY | 2008年 / 33卷 / 11期

关键词：

cocaine overdose rescue; addiction relapse; protein-based therapeutics for cocaine abuse; albumin fusion proteins; operant conditioning; drug self-administration rodent model;

D O I：

10.1038/sj.npp.1301666

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：2715 / 2725

页数：11

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