Inhibition of cytochrome P-450-dependent oxidation reactions by MAO inhibitors in rat liver microsomes.
The inhibition of cytochrome P-450 dependent hydroxylations of bufuralol (BH) and antipyrine, and O-deethylation of 7-ethoxycoumarin (7-ECOD) by several monoamine oxidase inhibitors (MAOIs) was investigated in rat liver microsomes. According to their IC50 values, clorgyline was the most potent inhibitor while toloxatone, the only reversible MAOI in this study, was the least potent. A great variability of inhibitory potencies was found, even in the same chemical class of MAOIs. Irreversible inhibition of BH and 7-ECOD has been studied. Rapid irreversible inhibition occurred in some cases, and this could be responsible for in vivo inhibition after repeated dosing of these MAOIs.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009249:NADP / Q000494:pharmacology; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D065607:Cytochrome P-450 Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; C043872:bufuralol 1'-hydroxylase; D000983:Antipyrine