Abstract
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.
Publication types
-
Comparative Study
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Behavior, Addictive / enzymology*
-
Behavior, Addictive / prevention & control*
-
Butyrylcholinesterase / chemistry
-
Butyrylcholinesterase / genetics
-
Butyrylcholinesterase / pharmacology*
-
CHO Cells
-
Cocaine / administration & dosage
-
Cocaine / antagonists & inhibitors*
-
Cocaine / toxicity*
-
Cricetinae
-
Cricetulus
-
Dose-Response Relationship, Drug
-
Female
-
Humans
-
Hydrolases / chemical synthesis
-
Hydrolases / genetics
-
Hydrolases / pharmacology*
-
Male
-
Motor Activity / drug effects
-
Motor Activity / physiology
-
Protein Engineering / methods
-
Rats
-
Rats, Sprague-Dawley
-
Rats, Wistar
-
Self Administration
Substances
-
Hydrolases
-
Butyrylcholinesterase
-
Cocaine