Disease relevance of Ecgonine

• Sixty- five fatal intoxications due to cocaine alone or in combination with other drugs were studied, and average blood levels were found to be higher in the deaths related to cocaine alone (e.g. 0.40 micro g ml(-1) for cocaine, 2.38 micro g ml(-1) for benzoylecgonine and 0.38 micro g ml(-1) for ecgonine methyl ester) [1].
• The effects of dietary supplements of cocaine, ecgonine methyl ester, a coca leaf extract and powdered coca leaves on body weight and overall body metabolism were studied in the rat [2].

High impact information on Ecgonine

• This vasoconstriction corresponded temporally with an increasing blood concentration of cocaine's main metabolites, benzoylecgonine and ethyl methyl ecgonine [3].
• Consistent with accelerated catalysis, the hydrolysis product ecgonine methyl ester was increased >10-fold in plasma of rats receiving mAb 15A10 and lethal amounts of cocaine [4].
• The authors developed a technique by which cocaine metabolites as well as cocaethylene can be identified and quantitated using gas chromatography/mass spectrometry (GC/MS), and deuterated standards of benzoylecgonine, cocaine, ecgonine methyl ester, and cocaethylene as internal standards [5].
• An inducible esterase catalyzing the hydrolysis of cocaine to ecgonine methyl ester and benzoic acid was identified and purified 22-fold [6].
• In vitro stability of cocaine in whole blood and plasma including ecgonine as a target analyte [7].

Biological context of Ecgonine

• Benzoylecgonine, but not ecgonine, could also be determined by reduction and subsequent acylation [8].
• The hydrolytic cleavage of the other ester group, methyl ester, to benzoyl ecgonine occurs spontaneously at body temperature [9].
• During chronic oral dosing, there appeared to be a trend for AUC ratios (AUCmetabolite/AUCcocaine) of benzoylecgonine and ecgonine methyl ester to decrease and norcocaine to increase, indicating the possibility of dose-, time-, or route-dependent changes in the absorption and/or metabolism of cocaine [10].
• Effect of Erythroxylum coca, cocaine and ecgonine methyl ester as dietary supplements on energy metabolism in the rat [2].

Anatomical context of Ecgonine

• Solid-phase extraction and GC/MS quantitation of cocaine, ecgonine methyl ester, benzoylecgonine, and cocaethylene from meconium, whole blood, and plasma [11].
• Other cocaine analytes frequently detected included ecgonine methyl ester and m-hydroxy-benzoylecgonine in amniotic fluid specimens and ecgonine methyl ester, norcocaine, and m-hydroxybenzoylecgonine in umbilical cord tissue specimens [12].
• A method was developed for measuring cocaine and its metabolites, benzoylecgonine, ecgonine methyl ester, norcocaine, ecgonine ethyl ester, cocaethylene, and m-hydroxybenzoylecgonine, in breast milk by gas chromatography/mass spectrometry [13].

Associations of Ecgonine with other chemical compounds

• The lack of correlation of substrate hydrolysis with the binding affinity of 70 catalytic antibodies was also observed for (-)-cocaine hydrolysis using derivatization and HPLC analysis of methyl ecgonine as meta-nitrococaine [14].
• The following analytes were identified and measured in meconium and urine: anhydroecgonine methyl ester; ecgonine methyl ester; ecgonine ethyl ester; cocaine; cocaethylene; benzoylecgonine; norcocaine; norcocaethylene; benzoylnorecgonine; m-and p-hydroxycocaine; and m-and p-hydroxybenzoylecgonine [15].

Gene context of Ecgonine

• In humans, the plasma enzyme, butyrylcholinesterase (E.C. 3.1.1.8), metabolizes cocaine to the water-soluble, pharmacologically inactive compounds, ecgonine methylester and benzoic acid [16].
• RESULTS: Butyrylcholinesterase enhanced cocaine metabolism to ecgonine methyl ester [17].
• The Br-DMEQ derivatives of BE and EC were separated on a C18 column and detected at 455 nm with excitation at 370 nm [18].
• Furthermore, our studies in the cat have also shown that purified BChE shifts the metabolic profile of cocaine (1 mg/kg) to the pharmacologically inactive products ecgonine methylester and ecgonine [19].

Analytical, diagnostic and therapeutic context of Ecgonine

• Additionally, fresh plasma samples containing either benzoylecgonine (BZE), ecgonine methyl ester (EME) or ecgonine (ECG) were stored at 4 degreesC and 20 degreesC [7].
• These results indicate that ecgonine methyl ester is a prominent urinary metabolite after street use of cocaine, which primarily involves intranasal application and intravenous injection rather than ingestion [20].
• In this study, cocaine, benzoylecgonine, and ecgonine methyl ester excretion in urine was measured after intravenous and intranasal administration of cocaine at 16, 32, 48, and 96 mg doses to healthy cocaine users [21].

References