Effects of chronic phenelzine in the rat: altered tissue weights and metabolism of 14C-phenelzine.

Phenelzine (2-phenylethylhydrazine, PZ, Nardil) a clinically important antidepressant, inhibits several enzyme systems including monoamine oxidase (MAO). Since PZ is itself a known substrate for MAO, it is possible that its metabolites will differ according to the functional status of MAO. We have, therefore, examined aspects of the metabolism of 14C-PZ in the rat after multiple (15 days) treatments with nonlabelled PZ and compared results to those obtained from drug naive animals. In addition, we have examined the effects of PZ treatment upon total body weight and the weights of selected organs. Total body weights and weights of lungs, livers and kidneys were reduced from controls after repeated injection with PZ. The excretion of radioactivity was also altered. The PZ-pretreated animals excreted less (p less than 0.05) radioactivity in urine (41.1 +/- 5.6 vrs 59.2 +/- 3.7% of dose in controls) and more in expired air (p less than 0.05) than did controls. These data suggest that prior treatments with PZ alter the metabolism and excretion of subsequently administered 14C-PZ.