A new and extremely rapid inducer of a cytochrome P-450-dependent monooxygenase species in rat liver microsomes.
The effect of Sulmazol, a new and extremely fast acting inducer of cytochrome P-450-dependent monooxygenase on rat liver microsomes is described. Actinomycin D prevented the induction by 60%. Despite a dramatic increase of monooxygenase activity no increase of cytochrome P-450 content could be observed. The induced P-450 species has not been identified yet; it has to possess very high specific activity, since increases of monooxygenase greater than 10-fold have been observed within 12 hours; the average increase is about 6-fold. The time course and the persistence of the induction after a single administration have been measured. Sulmazol is a strong competitive inhibitor of 7-ethoxycoumarin dealkylase activity with Ki = 1.1 muM. The main metabolite formed with microsomes of induced animals or in hepatocytes is a sulfoxidized compound rather than a hydroxylated derivative.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D003577:Cytochrome P-450 Enzyme System; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000201:enzymology*; D010105:Oxygenases / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007093:Imidazoles; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; C029758:sulmazole