7−Ethoxy−3,4−dimethylcoumarin: A Substrate for a Cytochrome p450-mediated Mono-oxygenase Activity that is Highly Induced by Phenobarbitone and β-Naphthoflavone

Abstract

Abstract The O-dealkylation of 7−ethoxy−3,4−dimethylcournarin in rat liver microsomes was catalysed in a typical cytochrome P450−mediated reaction as judged by cofactor requirement and inhibition criteria, and displayed monophasic Michaelis-Menten kinetics. When measured at low substrate concentration, this activity was highly inducible by treatment with phenobarbitone or β-naphthoflavone (44−and 78−fold induction, respectively). These data indicate the potential usefulness of this activity as a probe for P4501A1−and P4502B-mediated activities. The O-dealkylation of 7−methoxy-and 7−propoxy−3,4−dimethylcoumarin were much less inducible.