Abstract
Butyrylcholinesterase (BChE) is known to metabolize cocaine in humans. In the present study, three different experiments were performed to determine whether the addition of horse serum-derived BChE would accelerate the metabolism of cocaine. In the first experiment, the addition of BChE to squirrel monkey plasma in vitro reduced the half-life of cocaine by over 80%, decreased the production of the metabolic product benzoylecgonine, and increased ecgonine methyl ester formation. The effect of BChE on cocaine metabolism was reversed by a specific BChE inhibitor. In the second, in vivo, experiment, exogenously administered BChE reduced peak cocaine concentrations when given to anesthetized squirrel monkeys. Finally, incubation of cocaine with added BChE in human plasma in vitro resulted in a decrease in cocaine half-life similar to that observed with squirrel monkey plasma. The magnitude of the decrease in cocaine half-life was proportional to the amount of added BChE. Together, these results indicate that exogenously administered BChE can accelerate cocaine metabolism in such a way as to potentially lessen the behavioral and toxic effects of cocaine. Therefore, BChE may be useful as a treatment for cocaine addiction and toxicity.
Footnotes
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Send reprint requests to: Gilberto N. Carmona, Behavioral Neuroscience Branch, Preclinical Pharmacology Section, National Institutes of Health/National Institute on Drug Abuse Intramural Research Program, 5500 Nathan Shock Dr., Baltimore, MD 21224. E-mail: gcarmona{at}intra.nida.nih.gov
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Supported by National Institute on Drug Abuse Intramural Research Funds. Portions of the data were presented in abstract form at the College on Problems of Drug Dependence 57th Annual Scientific Meeting, Scottsdale, Arizona, 1995, and the meeting Peripheral Blockers as Treatments for Substance Abuse and Dependence. National Institutes of Health, National Institute on Drug Abuse, Rockville, Maryland, 1998.
- Abbreviations used are::
- BChE
- butyrylcholinesterase
- BE
- benzoylecgonine
- EME
- ecgonine methyl ester
- Iso-OMPA
- tetraisopropyl pyrophosphoramide
- GC-MS
- gas chromatography-mass spectrometry
- Received May 24, 1999.
- Accepted December 7, 1999.
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