Norcocaine

Cocaine-mediated hepatotoxicity has been associated with the conversion of cocaine to norcocaine and further oxidation products. The enzymes involved in in vitro hepatic oxidative N-demethylation of cocaine (192) were investigated (237), and two different enzymatic pathways appear to be important in the formation of the hepatotoxic metabolite. Cytochrome P-450 monooxygenases accomplish the direct N-demethylation of cocaine to norcocaine (194) as confirmed by induction and inhibition studies (Scheme 42). The second pathway for cocaine N-demethylation involves formation of cocaine /V-oxide (193) as an intermediate and two enzymes. A flavin-containing monooxygenase is first thought to convert cocaine to cocaine /V-oxide, followed by cytochrome P-450-... 

This local anaesthetic was photodemethylated in an organic chemical experiment. The cocaine (231) was irradiated at 300 nm in methanol for 43 h under nitrogen to give a 20% yield of norcocaine (232) [145],... 

The standard urine immunoassay for detection of cocaine (23a) abuse during the gestation period of newborn babies was frequently found to yield negative results in cases where positive results were shown by extraction of meconium with a solvent, followed by HPLC. The drug and metabolites such as norcocaine (23b) and cocaethyline (23c) were detected140. See Section IV.C for an alternative analysis of cocaine. 

D. J. Stewart, T. Inaba, M. Lucassen, W. Kalow, Cocaine Metabobsm - Cocaine and Norcocaine Hydrolysis by Liver and Serum Esterases , Clin. Pharmacol. Ther. 1979, 25, 464-468. 

Cocaine may be TV-demethyl ate d by the cytochrome P450 system to produce an active metabolite, norcocaine. Further breakdown produces A-hydroxynorcocaine and norcocaine nitroxide. Further metabolism produces a highly reactive free radical that is thought to be responsible for the hepatotoxicity observed in cocaine users.1... 

The most serious toxic effects of cocaine involve changes in the cardiovascular system. These include cardiac arrhythmias, myocardial ischaemia and infarction, and cerebrovascular spasm, all of which can be largely explained by the facilitation of the action of catecholamines on the cardiovascular system. Another explanation of the cardiotoxicity of cocaine lies in the direct vasoconstrictive properties of its major metabolite, norcocaine. It seems likely... 

EME and BEG, which is mainly obtained by enzymatic hydrolysis, represents respectively the 32-49 % and 29 45 % of total urinary metabolites cocaine can be converted, in small amounts, to norcocaine (NCOC) and psychoactive metabolite norbenzoylecgonine (NBE). The combined intake of alcohol and cocaine determines the formation of a pharmacologically active metabolite, the cocaethylene (ethyl ester of benzoylecgonine, CE), with a significant liver toxicity [13],... 

Cocaine was, and still is, in the focus of investigations.24-27,29-39 Amongst others, the mechanism of acute cocaine intoxication,24 behavioural sensitization,25 the effects of electric shock on responding, when maintained by cocaine,26 its effects in sleep-deprived humans,27 and the discriminative stimulus properties of cocaine, norcocaine, and A-allylnorcocaine32 have been studied. The effect of benzotropine mesylate on the prolactin response to haloperidol was observed.28... 

The authors noted that thrombotic microangiopathy due to cocaine is fairly rare. Its pathogenesis is unclear, possible mechanisms being an immune reaction or direct damage to the vascular endothelium. Cocaine-induced acute hepatitis has been linked to several toxic metabolites, including norcocaine and N-hydroxynorcocaine, which are produced by cytochrome P450 enzymes. 

Janzen, K., Concerning norcocaine, ethylbenzoylecgonine, and the identification of cocaine use in human hair, /, Anal. Toxicol., 16, 402, 1992. 

The metabolic scheme of cocaine analytes in hair. (Abbreviations COC, cocaine BE, benzoylecgonine EME, ecgonine methyl ester ECG, ecgonine CE, cocaethylene NCOC, norcocaine NCE, norcocaethylene and AEME, anhydroecgonine methyl ester). 

Cone et al. Cocaine users 6.4-19.2 0.3-2.5 0-1.9 (ecgonine methyl ester) 0-2.6 (cocaethylene) 0-0.7 (norcocaine) 0-trace (norcocaethylene) 1... 

Other definitive metabolites which are used in our laboratory as indicators of drug use are cocaethylene, norcocaine, A9-carboxy-tetrahydrocaimabinol (carboxy-THC) (a substance which is not found in smoke from a marijuana cigarette), and the heroin metabolites 6-MAM and morphine glucuronide. Drugs and metabolites are measured by ultrasensitive GC/MS/MS or chemical ionization ion-trap GC/MS techniques requiring 5 mg or less of sample. ... 

Gas Chromatography-Mass Spectrometry. In biological samples cocaine, benzoylecgonine and norcocaine, sensitivity 5 ng/ml—D. M. Chinn et al., J. analyt. Toxicol., 1980, 4, 37-42. 

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