The Antidepressant/Antipanic/Neuroprotective Drug Phenelzine: Neuropharmacological and Drug Metabolism Studies

Abstract: Phenelzine (PLZ) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic and neuroprotective properties. Metabolites of PLZ were investigated in rat brain. Levels of phenylacetic acid (PAA) and β-phenylethylamine (PEA) were found to be elevated after administration of PLZ and PEH (a major metabolite of PLZ) to rats, but the effect was greater with PLZ in both cases. Acute administration of PLZ or PEH increased brain levels of alanine (ALA) and GABA and decreased glutamine (GLN) levels. When MAO was inhibited prior to PLZ administration, levels of GABA and ALA were not increased, supporting the idea that the metabolite PEH formed by MAO is responsible for the increases. Chronic PLZ administration significantly reduced weight gain in rats, and brain levels of amino acids were quite different after 1 and 3 weeks of PLZ administration, perhaps as a result of its decreased metabolism to PEH with time.