DEXTROMETHORPHAN O-DEMETHYLASE ACTIVITY IN RAT-BRAIN MICROSOMES

CYP2D, a genetically variable isoform of cytochrome P450, has been cha racterized mainly in the liver and the brain of mammals by measurement of debrisoquine hydroxylase activity. Moreover, 'poor debrisoquine me tabolizer' phenotype is significantly increased in Parkinson's disease patients. We present here the first demonstration that the activity o f the CYP2D isoform can be characterized in rat brain microsomes by th e measurement of dextromethorphan O-demethylase capacity. The cerebral formation of dextrorphan, an antagonist of the N-methyl-D-aspartate r eceptor, was inhibited by the presence of quinidine and N-methyl-4-phe nylpyridinium (MPP(+)), a dopaminergic neurotoxin inducing a chemical parkinsonism in humans.