Effect of nifedipine, verapamil and diltiazem on the enzyme-inducing activity of phenobarbital and beta-naphthoflavone.
1. The effects of three calcium antagonists (CA), nifedipine (NF), verapamil (V) and diltiazem (DL) on the enzyme-inducing activity of phenobarbital (PB) and beta-naphthoflavone (beta-NF) were measured by hexobarbital (HB) sleeping time, benzphetamine-N-demethylase (BND) ethoxycourmarin-O-deethylase (ECOD) and ethoxyresorufin-O-deethylase (EROD) activities, as well as by the cytochrome P-450 and cytochrome b5 content. 2. NF, V and DL at oral doses of 100, 80 and 60 mg/kg administered 1 hr before PB additionally shortened the HB sleeping time. 3. Single administration of calcium antagonists on the background of developed PB-provoked enzyme induction prolonged the PB-shortened hexobarbital sleeping time. 4. Three day administration of NF, V and DL plus PB slightly decreased the enzyme-inducing effect of PB on BND activity and cytochrome P-450 and cytochrome b5 content. 5. NF and V administered only once after PB-provoked enzyme induction increased the PB enzyme-inducing effect on BND activity and on the content of cytochrome P-450. DL decreased the PB-induced BND activity and cytochrome P-450 and cytochrome b5 content. 6. The calcium antagonists studied affected the enzyme-inducing activity of beta-NF to a lesser extent when compared to PB. Only NF was found to potentiate the enzyme-inducing effect of beta-NF on the EROD activity and on the cytochrome P-450 content.
Koleva
M R
MR
Institute of Physiology, Bulgarian Academy of Sciences, Sofia.
Stoychev
T S
TS
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004110:Diltiazem / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D010088:Oxidoreductases / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology*; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D014700:Verapamil; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D004110:Diltiazem; D009543:Nifedipine; D010634:Phenobarbital