Hydroxylation of phenylethylamine by rat liver preparations. Inhibition studies

1. Rat liver 100,000 g pellet microsomal fraction p-hydroxylate phenylethylamine to tyramine in a relatively slow proceeding, NADPH-requiring reaction; Km 2.1 x 10(-5) M and Vmax 0.32 nmol/mg protein/20 min. 2. This reaction is inhibited, either competitively, noncompetitively or uncompetitively by a number of behaviorally active monomethylated and monohalogenated derivatives of phenylethylamine. 3. Whereas formation of tyramine was not significantly affected by L-phenylalanine or its p-chloro derivative, it was competitively inhibited by imipramine, iprindole and alprazolam. 4. It is suggested that at least some of the effects of these drugs may result from their ability to interfere with phenylethylamine metabolism.