Butyrylcholinesterase accelerates cocaine metabolism: In vitro and in vivoeffects in nonhuman primates and humans

Butyrylcholinesterase (BChE) is known to metabolize cocaine in humans. In t he present study, three different experiments were performed to determine w hether the addition of horse serum-derived BChE would accelerate the metabo lism 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%, decrea sed the production of the metabolic product benzoylecgonine, and increased ecgonine methyl ester formation. The effect of BChE on cocaine metabolism w as reversed by a specific BChE inhibitor. In the second, in vivo, experimen t, exogenously administered BChE reduced peak cocaine concentrations when g iven 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 c an 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.