A Cocaine Hydrolase Engineered from Human Butyrylcholinesterase Selectively Blocks Cocaine Toxicity and Reinstatement of Drug Seeking in Rats
| Autor: | Yang Gao, Luke A. Gliddon, Qinghai Zhao, David LaFleur, M Singh, Justin J. Anker, Stephen Brimijoin, Marilyn E. Carroll, Rutul R. Shah |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Drug Cocaine Esterase Hydrolases media_common.quotation_subject Self Administration CHO Cells Motor Activity Pharmacology Protein Engineering Article Rats Sprague-Dawley Cricetulus Cocaine Cricetinae Hydrolase Animals Humans Medicine Rats Wistar Butyrylcholinesterase media_common Dose-Response Relationship Drug business.industry Addiction Albumin Rats Behavior Addictive Psychiatry and Mental health Toxicity Female Self-administration business |
| Zdroj: | Neuropsychopharmacology. 33:2715-2725 |
| ISSN: | 1740-634X 0893-133X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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