Isotopic sensitivity in the microsomal oxidation of the dihydropyridine calcium entry blocker nifedipine

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.