Butyrylcholinesterase accelerates cocaine metabolism: in vitro and in vivo effects in nonhuman primates and humans.
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.
Carmona
G N
GN
Preclinical Pharmacology Section, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. gcarmona@intra.nida.nih.gov
Jufer
R A
RA
Goldberg
S R
SR
Gorelick
D A
DA
Greig
N H
NH
Yu
Q S
QS
Cone
E J
EJ
Schindler
C W
CW
D000818:Animals; D002091:Butyrylcholinesterase / Q000097:blood / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003042:Cocaine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D009294:Narcotics / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D012453:Saimiri; D013770:Tetraisopropylpyrophosphamide / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D009294:Narcotics; D013770:Tetraisopropylpyrophosphamide; D002091:Butyrylcholinesterase; D003042:Cocaine; C034524:ecgonine methyl ester