Brain cytochrome p450 distribution

The CNS contains much smaller amounts of drug-metabolizing enzymes than does the liver. The concentrations of the main enzymes in the brain, members of the cytochrome P450 (CYP) superfamily, are only 0.25% of concentration in the liver. But the brain enzymes are not uniformly distributed, as they are in the liver they are concentrated in specific brain areas. Theoretical models have explained that drug metabolism in the CNS cannot influence drug distribution in the blood, but there are marked differences in brain tissue levels depending on the presence... 

Abdelgadir SE, Roselli CE, Choate JV, Resko JA. 1997. Distribution of aromatase cytochrome P450 messenger ribonucleic acid in adult rhesus monkey brains. Biol Reprod 57 ... 

Bergh AF, Strobel HW. 1996. Anatomical distribution of NADPH-cytochrome P450 reductase and cytochrome P4502D forms in rat brain effects of xenobiotics and sex steroids. Mol Cell Biochem 162 31-41. 

McFadyen MC, Melvin WT, Murray GI. 1998. Regional distribution of individual forms of cytochrome P450 mRNA in normal adult human brain. Biochem Pharmacol 55 825-830. 

Morse DC, Stein AP, Thomas PE, Lowndes HE. 1998. Distribution and induction of cytochrome P450 lAl and 1A2 in rat brain. Toxicol Appl Pharmacol 152 232-239. 

Roselli CE, Resko JA. 2001. Cytochrome P450 aromatase CYP19) in the non-human primate brain distribution, regulation, and functional significance. J Steroid Biochem Mol Biol 79 247-253. 

Sanghera MK, Simpson ER, McPhaul MJ, Kozlowski G, Conley AJ, et al. 1991. Immunocytochemical distribution of aromatase cytochrome P450 in the rat brain using peptide-generated polyclonal antibodies. Endocrinology 129 2834-2844. 

Phenobarbital is utilized as a daytime sedative and anticonvulsant. It also induces several cytochrome P450 isozymes. Compared to other barbiturates, phenobarbital has a low oil/water partition coefficient, which results in slow distribution into the brain. It is available for oral, intravenous, or intramuscular administration. Doses for epileptic patients range from 60 to 200 mg per day. After a single oral dose of 30 mg, peak serum concentrations averaged 0.7 mg/L (n = 3). Repeated doses over a period of 7 days resulted in an average peak concentration of 8.1 mg/L.6 Chronic administration of 200 mg per day as anticonvulsant medication resulted in an average blood concentration of 29 mg/L (range = 16 to 48 mg/L).8... 

The relatively high affinity of these chemicals for lipid-rich tissues (Lipniak and Brandys, 1993) leads to disposition of B(a)P in rodent brain regions (Das et al, 1985). The intra-regional distribution of cytochrome P450 in brain tissues contributes to quantitative differences in PAH metabolite levels (Saunders et al, 2002 Brown et al, 2007). Several... 

Tissue Distribution Though they are most densely distributed in the liver and the intestines, GYP enzymes that are responsible for xenobiotic metabolism are also found in the placenta, lung, lymphocytes, macrophages, kidney, and even the brain. Most of the cytochromes P450 that process xenobiotics are located within the endoplasmic reticulum. The membrane phospholipids to which the enzymes are anchored... 

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