Formation of beta-phenylethylamine from the antidepressant, beta-phenylethylhydrazine

To determine whether the monoamine oxidase inhibitor phenelzine was metabolized in vivo to produce beta-phenylethylamine (PE) and p-hydroxy-beta-phenylethylamine [p-tyramine (pTA)], a deuterated analogue, alpha, alpha,, beta, beta-2H-phenelzine (d4-phenelzine) was synthesized and injected i.p. into rats. In the first experiment, rat striata from d4-phenelzine-treated rats were analyzed for the presence of d4-PE and d4-pTA at a time at which phenelzine was known to cause particularly large increases in striatal pTA. While d4-PE was found to be present in these rat striata at a concentration equivalent to the endogenous PE, no d4-pTA was present. The amounts of d4-PE produced at various times after the i.p. injection of 50 mg/kg d4-phenelzine were measured; at 1 hr post-injection, 371 +/- 60, 1295 +/- 682 and 1242 +/- 394 ng/g (mean +/- S.E.M.) d4-PE were present in whole brain, liver and kidney. Rat urine collected for a 24-hr period after this treatment contained (mean +/- S.E.M.) 88.5 +/- 14.0 micrograms d4-PE. These results clearly indicate that the antidepressant phenelzine was metabolized in vivo to produce the trace amine PE.