Product inhibition of aminopyrine N-demethylation in isolated hepatocytes.
The product inhibition of aminopyrine (AM) N-demethylation by 4-monomethylaminoantipyrine (MAA) was examined in vitro in preparations of isolated rat hepatocytes using gas chromatograph-mass spectrometer (GC-MS). The kinetic study for AM N-demethylation, which was determined by MAA formation, was studied at concentrations from 0.2 to 4.0 mM with or without various concentrations of D3-MAA. D3-MAA inhibited AM N-demethylation non-competitively at concentrations of 0.2 to 1.0 mM of AM (Ki = 0.81 mM), though it did competitively at concentrations of 1.0 to 4.0 mM of AM (Ki = 0.81 mM). From the present observation, it was suggested that the inhibition type of AM N-demethylation by D3-MAA was dependent on the substrate (AM) concentration.
D000632:Aminopyrine / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors*; D000818:Animals; D003640:Dealkylation; D004177:Dipyrone / Q000031:analogs & derivatives / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D047069:Pyrazolones; D051381:Rats; D011919:Rats, Inbred Strains
D007202:Indicators and Reagents; D047069:Pyrazolones; D000632:Aminopyrine; D004177:Dipyrone; D000633:Aminopyrine N-Demethylase; C008667:noramidopyrine