title: Dextromethorphan O-demethylase activity in rat brain microsomes.
abstract: CYP2D, a genetically variable isoform of cytochrome P450, has been characterized mainly in the liver and the brain of mammals by measurement of debrisoquine hydroxylase activity. Moreover, 'poor debrisoquine metabolizer' phenotype is significantly increased in Parkinson's disease patients. We present here the first demonstration that the activity of the CYP2D isoform can be characterized in rat brain microsomes by the measurement of dextromethorphan O-demethylase capacity. The cerebral formation of dextrorphan, an antagonist of the N-methyl-D-aspartate receptor, was inhibited by the presence of quinidine and N-methyl-4-phenylpyridinium (MPP+), a dopaminergic neurotoxin inducing a chemical parkinsonism in humans.
authors.affiliation: URA CNRS No. 597, Centre du Médicament, Nancy, France.
authors.forename: C
authors.initials: C
authors.lastname: Jolivalt
authors.forename: A
authors.initials: A
authors.lastname: Minn
authors.forename: M
authors.initials: M
authors.lastname: Vincent-Viry
authors.forename: M M
authors.initials: MM
authors.lastname: Galteau
authors.forename: G
authors.initials: G
authors.lastname: Siest
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000502:physiology*; D010090:Oxidoreductases, O-Demethylating / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011725:Pyridines; D003577:Cytochrome P-450 Enzyme System; D010090:Oxidoreductases, O-Demethylating; C052861:dextromethorphan O-demethylase; D011802:Quinidine; C023666:pyridine