The Rhodococcus sp. cocaine esterase: a bacterial candidate for novel pharmacokinetic-based therapies for cocaine abuse.
Cocaine is a powerful central nervous stimulant and among the most abused of drugs. Despite decades of efforts, however, no effective pharmacological treatments are available against cocaine addiction or toxic effects. Classical receptor-antagonist therapeutic approaches have not yielded significant effects, although cocaine targets are well known, thus fostering development of alternative therapeutic strategies. Recent evidence indicates that a sensible approach for treatment of cocaine abuse could be to interfere with cocaine pharmacokinetics, i.e. by preventing the drug from reaching the receptors responsible for its biological effects. Administration of cocaine binding antibodies as well as catalytic antibodies and enzymes that hydrolyze cocaine represent potential alternative therapeutic approach(es). The discovery of the cocaine esterase from the strain MBI of the bacterium Rhodococcus sp. (cocE) could be a major breakthrough in this field; cocE hydrolyzes cocaine faster than any known cocaine esterase and catalytic antibody.
Ascenzi
Paolo
P
Department of Biology, University Roma Tre, Viale G. Marconi 446, I-00146 Roma, Italy. ascenzi@uniroma3.it
Clementi
Emilio
E
Polticelli
Fabio
F
D043182:Carboxylesterase / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D002384:Catalysis; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000628:therapy*; D006801:Humans; D006868:Hydrolysis; D008099:Liver / Q000201:enzymology; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D012240:Rhodococcus / Q000201:enzymology* / Q000378:metabolism
D002265:Carboxylic Ester Hydrolases; C019921:cocaine esterase; D043182:Carboxylesterase; D003042:Cocaine