RT Journal Article
SR Electronic
T1 Free radical pathways in the in vitro hepatic metabolism of phenelzine.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 213
OP 219
VO 31
IS 2
A1 P R Ortiz de Montellano
A1 M D Watanabe
YR 1987
UL http://molpharm.aspetjournals.org/content/31/2/213.abstract
AB The in vitro metabolism of phenelzine (2-phenylethylhydrazine) by phenobarbital-pretreated rat liver microsomes yields ethylbenzene, 2-phenylethanol, 2-phenylacetaldehyde, benzaldehyde, benzylalcohol, and toluene as metabolites. Isotopic studies demonstrate that the oxygen atom of 2-phenylethanol derives from molecular oxygen and that this alcohol is not produced by reduction of 2-phenylacetaldehyde. The rates of destruction of cytochrome P-450, accumulation of spin-trapped 2-phenylethyl radicals, and formation of ethylbenzene and 2-phenylethanol are the same for [1,1-2H]-2-phenylethylhydrazine as for the undeuterated substrate. Small primary isotope effects are observed, however, for the formation of 2-phenylacetaldehyde (kH/kD greater than 1) and benzaldehyde (kH/kD less than 1). Synthetic 2-phenylethylhydroperoxide is converted by liver microsomes to the same alcohol and aldehyde metabolites. The results indicate that the metabolism of phenelzine by rat liver microsomes proceeds primarily via the 2-phenylethyl radical.