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Ability of bacterial cocaine esterase to hydrolyze active cocaine metabolites, and function in the presence of commonly co‐abused drugs
Author(s) -
Brim Remy Leigh,
Sunahara Roger K,
Woods James H
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.764.4
Subject(s) - benzoylecgonine , pharmacology , toxicity , drug , chemistry , medicine , metabolite , biochemistry , organic chemistry
Cocaine toxicity is a widespread problem in the United States, responsible for over half a million emergency department visits in 2006 (DAWN, Pub No. (SMA) 08‐4339, 2006). There is currently no FDA‐approved direct pharmacotherapy for cocaine toxicity. To this end, we have developed a mutant bacterial cocaine esterase (CocE), which hydrolyzes cocaine into inert metabolites and has low immunogenic potential. CocE prevents cocaine‐induced cardiovascular and neurological toxicities in rodent models (Jutkiewicz, Ann Emerg Med 2009; Wood, Drug and Alcohol Dependence 2009). Here we describe the ability of CocE to hydrolyze the active cocaine metabolites norcocaine, cocaethylene and benzoylecgonine, and the resilience of CocE, in that it hydrolyzes cocaine in the presence of drugs commonly co‐abused with cocaine. CocE hydrolyzes norcocaine and cocaethylene with 58% and 45% of its catalytic efficiency for cocaine in vitro (respectively), as measured by a spectrophotometric assay. The catalytic efficiency of CocE is not affected by many commonly co‐abused drugs in vitro , including alcohol, phencyclidine, morphine and nicotine. Overall, these results suggest that CocE is a good candidate pharmacotherapy for cocaine toxicity in that it hydrolyzes cocaine along with toxic metabolites, and is not inhibited by high concentrations of commonly co‐abused drugs. Research supported by USPHS grants DA021416 and GM007767.