RT Journal Article
SR Electronic
T1 The opposing effects of N-hydroxyamphetamine and N-hydroxyphentermine on the H2O2 generated by hepatic cytochrome P-450.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 465
OP 470
VO 22
IS 2
A1 A K Cho
A1 M S Maynard
A1 R M Matsumoto
A1 B Lindeke
A1 U Paulsen
A1 G T Miwa
YR 1982
UL http://molpharm.aspetjournals.org/content/22/2/465.abstract
AB The effects of N-hydroxyphentermine (NOHP) and N-hydroxyamphetamine (NOHA) on hydrogen peroxide generated by rat liver microsomes and reconstituted preparations in the presence of NADPH were compared. In microsome incubations, NOHP caused an increase in H2O2 levels and NOHA caused a substantial decrease. When the substances were compared for cytochrome P-450-dependent H2O2 generation in reconstituted preparations, NOHA at mM blocked generation and NOHP had no effect. NOHP appears to be an uncoupler of the cytochrome P-450 system in microsomes whereas NOHA is a potent inhibitor, presumably because of its ability to form a metabolic intermediate complex. During the course of their effects on O2 reduction, NOHP and NOHA are themselves undergoing oxidation, NOHP to 2-methyl-2-nitro-1-phenylpropane and NOHA to phenylacetone oxime. The enzymatic natures of these oxidations differ. Thus, two closely related arylalkylhydroxylamines differ substantially in their interaction with cytochrome P-450 systems.