7-Ethoxy-3,4-dimethylcoumarin: a substrate for a cytochrome P450-mediated mono-oxygenase activity that is highly induced by phenobarbitone and beta-naphthoflavone.
The O-dealkylation of 7-ethoxy-3,4-dimethylcoumarin 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 beta-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.
Giurnazi
A M
AM
Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, UK.
Garle
M J
MJ
Lal
K
K
Fry
J R
JR
D000818:Animals; D003374:Coumarins / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D010477:Perfusion; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019324:beta-Naphthoflavone / Q000494:pharmacology*
C104179:7-ethoxy-3,4-dimethylcoumarin; D003374:Coumarins; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital