N-oxidation of phentermine to N-hydroxyphentermine by a reconstituted cytochrome P-450 oxidase system from rabbit liver.
Previous studies in our laboratory have indicated that the cytochrome P-450 system is involved in the oxidation of phentermine (2-methyl-1-phenyl-2-aminopropane) to N-hydroxyphentermine by liver microsomal preparations. In the present study, a reconstituted system which consisted of cytochrome P-450 and NADPH cytochrome P-450 reductase purified from liver microsomes of phenobarbital-induced rabbits was found to oxidize phentermine to N-hydroxyphentermine. The reaction was NADPH-dependent and required the presence of both the cytochrome P-450 and reductase preparations. N-Hydroxyphentermine was formed 3 times more rapidly in incubation mixtures which contained dilauroyl phosphatidylcholine than in those without added phospholipid. The reaction was inhibited several-fold by octylamine. It is concluded that the cytochrome P-450 system is able to catalyze the oxidation of phentermine to N-hydroxyphentermine.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology*; D003902:Detergents / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010645:Phentermine / Q000031:analogs & derivatives* / Q000378:metabolism*; D011817:Rabbits
D003902:Detergents; C013568:N-hydroxyphentermine; D003577:Cytochrome P-450 Enzyme System; D010645:Phentermine; D009251:NADPH-Ferrihemoprotein Reductase