What are the three major metabolites of cocaine? What active metabolite is also created in the presence of ethanol?
Approximately 5% of cocaine undergoes N-demethylation into norcocaine. Nearly half is both nonenzymatically and enzymatically hydrolyzed to form benzoylecgonine. Plasma cholinesterase and other esterases metabolize 32-49% of cocaine into ecgonine methyl ester. In the presence of ethanol, some cocaine undergoes transesterification with ethanol instead of hydrolysis with water producing the active metabolite ethylbenzoylecgonine, or cocaethylene.
Inaba T, et al. Metabolism of cocaine in man. Clin Pharmacol Ther . 1978;23:547–552. Dean RA, et al. Human liver cocaine esterases: ethanol-mediated formation of ethylcocaine. FASEB J. 1991;5:2735–2739.
Contributed by Catherine Dong, MD