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Background: Phenelzine (PLZ) is a non-specific monoamine oxidase inhibitor that has demonstratedclinical efficacy in patients with treatment resistant depression. The mechanism of action with regard to thisefficacy is complicated in that its metabolite, β-phenylethylidenehydrazine (PEH), is an inhibitor of aminoacid transaminases resulting in dramatic brain elevations of GABA, alanine, ornithine and tyrosine. The fullneurochemical profile of PLZ and PEH remain to be explored.Objective: To undertake a non-targeted metabolomics study of phenelzine on rat brain neurochemistry.Methods: We undertook a high-resolution mass spectrometric metabolomics analysis of rat cortical brain1 and 12 hours after intraperitoneal dosing with PLZ or PEH. Tandem mass spectrometry was utilized toobtain relative quantitation data.Results: N-acetyl amino acids were found to be elevated in cortical brain tissue following either PLZ orPEH treatments.Conclusions: Our data indicate PLZ treatment significantly augments brain levels of N-acetyl amino acidsand that this may involve inhibition of deacylases by PEH and/or induction of N-amino acidacetyltransferases.

neurology and neurobiology

Metabolomics of Rat Brain After Treatment with Phenelzine: High-Resolution Mass Spectrometric Demonstration of Increased Brain Levels of N-Acetyl Amino Acids