Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity.
One pharmacokinetic approach to the treatment of cocaine abuse and toxicity involves the development of compounds that can be safely administered to humans and that accelerate the metabolism of cocaine to inactive components. Catalytic antibodies have been developed and shown to accelerate cocaine metabolism, but their catalytic efficiency for cocaine is relatively low. Mutations of human butyrylcholinesterase and a bacterial cocaine esterase found in the soil of coca plants have also been developed. These compounds accelerate cocaine metabolism and antagonize the behavioral and toxic effects of cocaine in animal models. Of these two approaches, the human butyrylcholinesterase mutants show the most immediate promise as they would not be expected to evoke an immune response in humans.
Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Suite 200, Baltimore, MD 21224, USA. cschindl@helix.nih.gov
Charles W
CW
Schindler
Steven R
SR
Goldberg
D000818:Animals; D002091:Butyrylcholinesterase / Q000235:genetics; D002265:Carboxylic Ester Hydrolases / Q000235:genetics; D003042:Cocaine / Q000378:metabolism* / Q000633:toxicity; D019970:Cocaine-Related Disorders / Q000201:enzymology / Q000628:therapy*; D006801:Humans; D009154:Mutation
D002265:Carboxylic Ester Hydrolases; C019921:cocaine esterase; D002091:Butyrylcholinesterase; D003042:Cocaine