2002/11/07 by Anabel S. Fandiño, Stefan W. Toennes, Gerold F. Kauert · 1 citation
Pharmacology, Toxicology and Pharmaceutics · Biochemistry, Genetics and Molecular Biology · Medicine · #Pharmacogenetics and Drug Metabolism #Eicosanoids and Hypertension Pharmacology #Hormonal and reproductive studies
paper · doi:10.1021/tx0255828
openalex publication_date 2002/11/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/26
During smoking of cocaine-base (crack), anhydroecgonine methyl ester (AEME, methylecgonidine) is formed in large amounts as a pyrolysis product of cocaine and is absorbed in the lungs. The metabolism of AEME was studied in the present investigation using microsome preparations from rat liver, lung, kidney, and brain. Potential metabolites of AEME were synthesized and used as substrate to complement the experiments. Analysis of the incubation mixtures was performed using gas chromatography-mass spectrometry and nanoelectrospray multiple-stage mass spectrometry. Screening for metabolites was focused on postulated oxidative pathways, chemical and enzymatic hydrolysis, and ethanol dependent transesterification as known from cocaine metabolism. Enzymatic hydrolysis of AEME to anhydroecgonine (AE), which was inhibited by sodium fluoride, was found in all microsomal preparations. Liver microsomes exhibited the highest activity, brain microsomes the lowest. Anhydronorecgonine methyl ester (ANEME) and anhydroecgonine methyl ester N-oxide were identified as AEME metabolites of liver and lung microsomes only. In the presence of ethanol AEME was metabolized to anhydroecgonine ethyl ester and anhydronorecgonine ethyl ester. Further metabolism of AE or ANEME was not observed. No N-hydroxy-anhydronorecgonine derivatives were found which could represent precursors of cytotoxic metabolites as known to be formed from cocaine.