Liver monooxygenase activity after multiple application of nifedipin, verapamil and diltiazem

The effects of three calcium antagonists--nifedipin (NF), verapamil (V) and diltiazem (DL)--on the duration of hexobarbital (HB) sleeping time and on monooxygenase activity are studied. The drugs are applied in oral doses of 50, 40 and 30 mg/kg, respectively every day for 3 weeks on male albino rats. NF was found to shorten the duration of HB sleep, to increase the activities of EMD, BPD, AH, ECOD, EROD, NADPH-cytochtome P-450 reductase and the content of cytochrome P-450, and it does not change significantly the content of cytochrome b 5. It increases AD hydroxylation in positions 7-alpha-, 16-beta-, 16-alpha- and 6-beta, which suggests indirectly that NF has probably induced the synthesis of cytochrome P-450a, cytochrome P-450b, cytochrome P-450h and cytochrome P-450p, respectively. Verapamil also shortens the duration of HB sleeping time, increases the activities of EMD, BPD, AH, EROD and NADPH-cytochrome P-450 reductase, not changing the cytochrome P-450 content and the ECOD activity. It increases AD hydroxylation in positions 7-alpha- and 16-alpha-, which suggests probable induction of the synthesis of cytochrome P-450a and cytochrome P-450h. Unlike the other two calcium antagonists, diltiazem slightly shortens the duration of HB sleeping, not changing the enzyme activities studied, the content of cytochrome P-450 and cytochrome b 5, but increases the activities of EROD and NADPH-cytocrome P-450 reductase. It increases AD hydroxylation in positions 7-alpha-, 16-alpha- and 6-beta, which suggests probable induction of cytochrome P-450a, cytochrome P-450h and cytochrome P-450p.(ABSTRACT TRUNCATED AT 250 WORDS)