The Rhodococcus sp. Cocaine Esterase: A Bacterial Candidate for Novel Pharmacokinetic‐based Therapies for Cocaine Abuse

Abstract

SummaryCocaine 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 MB1 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. IUBMB Life, 55: 397-402, 2003 Keywords Rhodococcus sp. esterase; human plasma butyrylcholinesterase; human liver carboxylesterase-1; human liver carboxylesterase-2; cocaine binding antibodies; cocaine binding catalytic antibodies; cocaine metabolism.

PEGylation of bacterial cocaine esterase for protection against protease digestion and immunogenicity

“…Cocaine is a well known tropane alkaloid acting as a powerful central nervous stimulant and reinforcing drug [1]. Therefore, the abuse of cocaine continues to be a major societal and health problem [2].…”

A Novel Alkaline Esterase fromSporosarcinasp. nov. Strain eSP04 Catalyzing the Hydrolysis of a Wide Variety of Aryl-carboxylic Acid Esters

“…17,18) Aryl-carboxylesterases, however, have many potential applications in various fields. They are attractive biocatalysts for the production of various aromas, fragrances, 19,20) and preservatives, 17,18) for the selective removal of protecting groups, 21,22) and in the field of health [23][24][25][26] as well as being potentially beneficial for the environment. It is thus of great interest to obtain a new arylcarboxylesterase with broad or unusual substrate specificities.…”

Las enzimas involucradas en el metabolismo de la cocaína: Una nueva aproximación farmacológica para el tratamiento de la intoxicación por sobredosis de cocaína

“…95 La actividad enzimática de esta esterasa se logró incrementar hasta x1000 veces más en comparación con la mostrada por la hBChE humana, 105-106 veces más rápida que un anticuerpo monoclonal. 96 La administración de bCocE atenuó el restablecimiento de la conducta de búsqueda de la droga en animales entrenados previamente a auto-administrarse la cocaína y bloqueó el incremento en la actividad locomotora, inducido por ella. 97 Además, la bCocE, en dosis de 28 mg/kg, restauró rápidamente (tres minutos) la presión sanguínea, disminuyó la hipertensión, la arritmia cardiaca y redujo la toxicidad inducida por una sobredosis (100 mg/kg, ip.…”