Enhancing cocaine metabolism with butyrylcholinesterase as a treatment strategy.
Existing pharmacodynamic approaches to cocaine abuse treatment have not been widely successful. An alternative, pharmacokinetic, approach is to enhance cocaine metabolism by administration of butyrylcholinesterase (BChE), a major cocaine-metabolizing enzyme in primates. Initial studies in rodents suggest that BChE pretreatment can substantially reduce the acute physiological and behavioral effects of cocaine, at enzyme doses that themselves have no behavioral or toxic effects. A single enzyme injection may increase plasma BChE activity for several days, suggesting that exogenous administration may be practical. BChE treatment may also produce a favorable pattern of cocaine metabolites. Further research is needed to evaluate the long-term effects of BChE administration.
Gorelick
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DA
NIH/NIDA Division of Intramural Research, Treatment Branch, Baltimore, MD 21224, USA.
D000818:Animals; D002091:Butyrylcholinesterase / Q000097:blood / Q000494:pharmacology*; D003042:Cocaine / Q000493:pharmacokinetics*; D019970:Cocaine-Related Disorders / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D051381:Rats
D004791:Enzyme Inhibitors; D002091:Butyrylcholinesterase; D003042:Cocaine