ON THE ENZYME-INDUCING ACTION OF CALCIUM-ANTAGONISTS

The effects of three calcium antagonists, nifedipine (NF), verapamil ( V) and diltiazem (DL), on rat liver monooxygenases were studied. The d rugs were administered in oral doses of 50, 40 and 30 mg/kg daily for 3 weeks in male Wistar rats. NF and V shortened the hexobarbital (HB) sleeping time and increased benzphetamin-N-demethylase (BND), ethylmor phine-N-demethylase (EMND), aniline hydroxylase (AH), ethoxycoumarine- O-deethylase (ECOD), ethoxyresorufin-O-deethylase (EROD) and NADPH-cyt ochrome c reductase activities and the content of cytochrome P-450 and microsomal heme, but did not change the content of cytochrome b5. The data suggest that these calcium antagonists exert an enzyme-inducing effect on the hepatic monooxygenases. DL significantly increased only the EROD and NADPH-cytochrome c reductase activities and shortened HB sleeping time to a lesser extent, suggesting a weaker enzyme-inducing effect as compared to NF and V. The three drugs increased the delta-am inolevulinic acid (ALA) synthetase activity and decreased heme oxygena se (HO) activity. The increased cytochrome P-450 content is probably d ue to the increased synthesis and the decreased breakdown of this hemo protein.