Biochemical and Biophysical Research Communications
Cytochrome P-450 and NADPH cytochrome reductase in rat brain: Formation of catechols and reactive catechol metabolites
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The mechanisms of interactions of psychotropic drugs with liver and brain cytochrome P450 and their significance for drug effect and drug-drug interactions
2022, Biochemical PharmacologyCitation Excerpt :Cytochrome P450 (CYP) is a terminal oxidase in the mixed function oxidase system, mainly located in the endoplasmic reticulum of the liver, but also in other organs including the brain, where it is present in all cell membranes [1–6].
Cytochrome P450 enzymes and metabolism of drugs and neurotoxins within the mammalian brain
2022, Advances in PharmacologyCitation Excerpt :Similarly, the presence of CYP protein within the brain can be assessed and quantified using Western Blot, while various in situ and in cyto labelling techniques are applied to visualize the spatial distribution of CYP proteins within brain regions, tissues, and cells (Cheng et al., 2013; Chinta et al., 2005; Miksys, Rao, Hoffmann, Mash, & Tyndale, 2002; Ravindranath, Anandatheerthavarada, & Shankar, 1989). Assessing CYP metabolic activity in the brain is challenging due to low CYP protein levels overall and rapid degradation in brain tissue collected post-mortem (Sasame et al., 1977; Tyndale et al., 1999). Nevertheless, CYP enzymatic activity can be assessed in vitro in brain by quantifying enzymatic product formation following incubation of brain tissue with a CYP-selective substrate (Bhamre et al., 1993; Ravindranath et al., 1989; Tyndale et al., 1999).
CYP-mediated drug metabolism in the brain impacts drug response
2018, Pharmacology and TherapeuticsCitation Excerpt :Outside of this scope there have been substantial advancements in the research areas of additional CYPs within the brain (e.g. CYP17, CYP27, and CYP46), however we have focused on CYP1–4 due to their role in the metabolism of a broad range of clinically relevant central nervous system (CNS)-acting compounds, and the contrasting regulation of these CYPs in brain relative to that in liver. Early evidence of CYP activity in the brain came in the 1970s (Fishman, Hahn, & Norton, 1976; Paul, Axelrod, & Diliberto, 1977; Sasame, Ames, & Nelson, 1977), which was followed by research into subcellular localization, activity, and substrate specificity compared to liver CYP enzymes (Miksys & Tyndale, 2004). Substantial interest exists in brain CYPs due to the potentially unique impact of CYP-mediated metabolism within the brain (e.g. on the blood-brain barrier (BBB)).
Xenobiotic metabolizing enzymes in the central nervous system: Contribution of cytochrome P450 enzymes in normal and pathological human brain
2008, BiochimieCitation Excerpt :In this review we will focus on the nature and the distribution of the isoforms of CYPs in the human brain, and on the recent understanding of the role of these enzymes in brain physiology as well as in response to xenobiotics (drugs, toxic compounds) and in the pathogenesis of neurodegenerative disorders. The CYP brain content first evaluated in rat from microsomal preparations was of 30 pmol/mg of protein, which is approximately 3% of the corresponding level in the liver [4]. However the enzymes are not uniformly distributed among the different regions and cells of the brain and sex-related differences have also been reported.
Cytochrome P450-mediated drug metabolism in the brain
2013, Journal of Psychiatry and Neuroscience