Regular ArticleInactivation of Cytochromes P450 2B Protects Against Cocaine-Mediated Toxicity in Rat Liver Slices
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In vitro measurements of metabolism for application in pharmacokinetic modeling
2008, Pharmacology and TherapeuticsXenobiotic metabolizing enzymes in the central nervous system: Contribution of cytochrome P450 enzymes in normal and pathological human brain
2008, BiochimieCitation Excerpt :This compound is also O-demethylated by CYP2D6 into a toxic substance (4-hydroxyamphetamine) [53,54]. In addition, CYP2B6 metabolizes also psychoactive substances such as cocaine [55,56], phencyclidine [57] and some amphetamines [58]. Both CYP2B6 and CYP2D6 are inducible by nicotine: CYP2B6 is described as the enzyme mainly responsible for the metabolism of nicotine in brain of smokers [11], but CYP2D6 may influence the disposition of nicotine in the small subset of the population who correspond with CYP2D6 ultrametabolizer phenotype [59].
CYP2B6 is expressed in African Green monkey brain and is induced by chronic nicotine treatment
2006, NeuropharmacologyCitation Excerpt :The elevated brain CYP2B6 levels in smokers and in non-smokers exposed to second-hand smoke or in people treated with nicotine may contribute to the activation of nitrosamines to DNA adducts. In addition, CYP2B also metabolizes drugs of abuse such as cocaine (Poet et al., 1994), amphetamines, ecstasy (Kreth et al., 2000) and phencyclidine (Jushchyshyn et al., 2003). In smokers, some brain cells may be at greater risk for toxicity due to localized and induced drug metabolism depending on the relative toxicity and pharmacology of the parent drug and metabolism.
Induction of nicotine-metabolizing CYP2B1 by ethanol and ethanol-metabolizing CYP2E1 by nicotine: Summary and implications
2003, Biochimica et Biophysica Acta - General SubjectsInduction of CYP2B1/2 and nicotine metabolism by ethanol in rat liver but not rat brain
2001, Biochemical PharmacologyCitation Excerpt :CYP2B1/2 also metabolize cocaine to a toxic metabolite [9], suggesting additive or synergistic increases in liver damage when ethanol and cocaine are used concurrently. In fact, inhibition of CYP2B enzymes protects against cocaine-mediated hepatotoxicity in rats [9]. The mechanism(s) by which CYP2B enzymes are induced by ethanol is not known.
The effects of phencyclidine pretreatment on cocaine-mediated hepatotoxicity in mice
2001, Toxicology and Applied Pharmacology