title: Isotopic sensitivity in the microsomal oxidation of the dihydropyridine calcium entry blocker nifedipine.
abstract: The primary deuterium isotope effect on Vm for the microsomal oxidation of the dihydropyridine calcium entry blocker nifedipine [4-(2-nitrophenyl)-2,6-dimethyl-3,5- bis(methoxycarbonyl)-1,4-dihydropyridine] has been measured. The magnitude of the kinetic isotope effect, 6.7, suggests that the rate-limiting step in the mechanism of microsomal oxidation of nifedipine involves the loss of a hydrogen atom rather than nitrogen oxidation. Thus the microsomal oxidation of nifedipine is mechanistically different from that of other 1,4-dihydropyridines.
authors.affiliation: Toxicology Program, College of Pharmacy, University of New Mexico, Albuquerque 87131.
authors.forename: J L
authors.initials: JL
authors.lastname: Born
authors.forename: W M
authors.initials: WM
authors.lastname: Hadley
mesh_terms: D000818:Animals; D003903:Deuterium; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: C036128:dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate; D003903:Deuterium; D009543:Nifedipine