Disease relevance of Norcocaine

• Benzoylecgonine and ecgonine methyl ester did not produce toxic manifestations at infusion rates that produced toxicity in the cocaine, norcocaine, and cocaethylene groups [1].
• Pentobarbital anesthesia enhanced the respiratory depression and suppressed or delayed the onset of convulsions from norcocaine and cocaine infusion [2].
• There were no gender-related differences in the doses of norcocaine required to produce circulatory collapse; however, there were significant gender-related differences in the norcocaine tissue-to-plasma concentration ratios (T:P ratios) [3].

Psychiatry related information on Norcocaine

• A comparison of cocaine and its metabolite norcocaine: effects on locomotor activity [4].

High impact information on Norcocaine

• Cocaine (NCN) is first N-demethylated to norcocaine, followed by oxidation to N-hydroxynorcocaine (NCNOH) and norcocaine nitroxide (NCNO.). On the basis of ESR studies of NCNOH with rat liver microsomes, it has been proposed that NCNO. induces hepatotoxicity by futile redox cycling between NCNO. and NCNOH at the expense of NADPH [5].
• N-demethylation of cocaine to norcocaine. Evidence for participation by cytochrome P-450 and FAD-containing monooxygenase [6].
• Cocaine metabolism: cocaine and norcocaine hydrolysis by liver and serum esterases [7].
• The hydrolysis of cocaine and its N-demethylated product, norcocaine, by esterases was examined in liver and serum [7].
• The results indicate that norcocaine nitroxide is hepatotoxic and suggest the involvement of P450 enzymes [8].

Chemical compound and disease context of Norcocaine

• An isocratic high-performance liquid chromatographic method with ultraviolet detection at 235 nm is described for the determination of cocaine and its metabolites benzoylecgonine, norcocaine and ecgonine methyl ester in rat plasma, collected during toxicity studies [9].

Biological context of Norcocaine

• Biotransformation of norcocaine to norcocaine nitroxide by rat brain microsomes [10].
• Compared with cocaine, norcocaine and cocaethylene had more potent and prolonged effects on the neurochemical, heart rate, and QRS interval responses, and were equipotent in increasing the mean arterial blood pressure [11].
• Norcocaine did not affect heart rate at doses up to 3.0 mg/kg [12].
• The present study examined the pharmacokinetics of arterial plasma concentrations of cocaine and metabolite profile [benzoylecgonine (BE), ecgonine methyl ester (EME), norcocaine (NC)] following a single i.v. injection of 0.5, 1.0, or 3.0 mg/kg cocaine [13].
• Exposure of untreated cultures to COC or norcocaine (NOR) caused dose-dependent increases in LDH release, decreased protein synthesis, and eventual cell death [14].

Anatomical context of Norcocaine

• Meconium samples from sheep with and without esophageal ligation demonstrated high levels of norcocaine [15].
• Furthermore, induction of cytochrome P450-mediated cocaine or norcocaine metabolism was associated with inhibition of protein biosynthesis in cultured hepatocytes, whereas this effect was restored to normal when the oxidative metabolism was blocked by SKF-525A [16].
• 2. The biological t 1/2 of norcocaine (dose 2 mg/kg i.v.) in plasma, liver and brain were 0.4, 1.6, 0.5 h, respectively and the compound was not detectable in the central nervous system 6 h after injection [17].
• In vitro, the direct application of cocaine, norcocaine, and N-hydroxynorcocaine on isolated mitochondria had no effect on the ADP:O or respiratory control ratios, at concentrations up to 2.0 mM [18].

Associations of Norcocaine with other chemical compounds

• Electron microscopy revealed the presence of pronounced changes in cell morphology as early as 30 min after the norcocaine nitroxide dose [8].
• Liver microsomes from phenobarbital-induced BALB/cBy mice had less norcocaine N-hydroxylase activity than those from B6AF1 mice [19].
• The compounds were prepared by alkylation of norcocaine, which was obtained by demethylation of cocaine with 2,2,2-trichloroethyl chloroformate followed by zinc--acetic acid reduction [20].
• Phencyclidine (PCP) pretreatment did not increase either P450s 3A or 2B, yet it markedly enhanced cocaine- or norcocaine-induced serum ALT activity [21].
• Cocaine, norcocaine, ecgonine methylester and benzoylecgonine pharmacokinetics in the rat [22].

Gene context of Norcocaine

• Immunoinhibition studies showed that cytochrome P450 2A5 was the major isoform responsible for norcocaine N-hydroxylation [23].
• The metabolism of 1 mM cocaine correlated strongly with immunodetected CYP3A protein determined by Western blotting in both fetal (r = 0.89, p = 0.19) and adult specimens (r = 0.82, p < 0.01) . These findings further support CYP3A as a major catalyst of norcocaine formation in human liver microsomes [24].
• In this study we examined the kinetics of norcocaine N-hydroxylation mediated by cytochrome P450 (CYP) in mouse and human liver microsomes [25].
• The specific activities of norcocaine formation by microsomes prepared from three human liver samples correlated with the amount of P-450 3A immunoreactive protein detected by immunoblot [26].
• Since cocaine can be metabolized by both esterase and P-450 monooxygenase, we studied the direct effects of cocaine, benzoylecgonine and norcocaine on the in vitro T-dependent antibody response to SRBC [27].

Analytical, diagnostic and therapeutic context of Norcocaine

• Intravenous self-administration of cocaine and norcocaine by dogs [28].
• Contribution of the active metabolite, norcocaine, to cocaine's effects after intravenous and oral administration in rats: pharmacodynamics [29].
• Gas chromatography/mass spectrometry was essential to the identification of norcocaine, because norcocaine is frequently not identified [30].
• Identification and determination of norcocaine in illicit cocaine and coca leaves by gas chromatography-mass spectrometry and high-performance liquid chromatography [31].
• The HPLC elution of cocaine and norcocaine was performed using a Spherisorb RP-18, 100 mm x 4.6 mm I.D., 5 microns particle size column with a mobile phase containing acetonitrile-0.1% TMAHS aqueous solution (60:40) [32].

References