Biphasic effect of pyrazolone derivatives on drug-metabolizing enzyme in rat liver.
The pyrazolone derivatives aminophenazone, phenazone, and propyphenazone known as inducers are capable of inhibiting initially monooxygenase-dependent biotransformation steps. In the dose of 1.5 mmol X kg-1 they prolong the hexobarbital narcosis (max. 1 h after administration) due to a reduced hexobarbital metabolism in the liver. An influence on the N-demethylation (aminophenazone as substrate) ist not substantial. The catalytic binding site of cytochrome P-450 is not influenced. In aminophenazone- and phenazone-treated animals the inhibitory phase is followed by a stimulatory one. After the repeated administration the inhibitory phase continues up to the third measured 1 h after administration. The initially inhibitory effect of inducers seems to be caused by a mutual interference of a complete or partial binding to various forms of cytochrome P-450. However, effects on the CNS cannot be excluded.
D000632:Aminopyrine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D000983:Antipyrine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003640:Dealkylation; D005260:Female; D006591:Hexobarbital / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008862:Microsomes, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D000632:Aminopyrine; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D006899:Mixed Function Oxygenases; C009077:propyphenazone; D000983:Antipyrine; D010634:Phenobarbital