期刊
NEUROPSYCHOPHARMACOLOGY
卷 33, 期 11, 页码 2715-2725出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.npp.1301666
关键词
cocaine overdose rescue; addiction relapse; protein-based therapeutics for cocaine abuse; albumin fusion proteins; operant conditioning; drug self-administration rodent model
资金
- Minnesota Partnership for Medical Genomics and Biotechnology
- NIH/NIDA [R01-DA023979-01]
- Cogenesys Inc., Rockville, MD
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.
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