beta-phenylethylidenehydrazine, a novel inhibitor of GABA transaminase

Phenylethylidenehydrazine (PEH), a proposed metabolite of phenelzine (PLZ), was synthesized in our laboratories and administered to rats in a series o f time- and dose-response studies. Phenelzine is a monoamine oxidase (MAO) inhibiting antidepressant/antipanic drug that also causes marked elevations of brain levels of the inhibitory neurotransmitter (gamma -aminobutyric ac id (GABA). Like PLZ, PEH inhibited GABA transaminase (GABA-T) and caused ma rked, long-lasting increases in rat brain levels of GABA. The addition of t he double bond in PEH caused a marked decrease in its ability to inhibit MA O compared to PLZ. Given the ability of PEH to elevate GABA levels and its lack of significant effect on MAO, it may be a very effective and safe tool with which to study the role of GABA in anxiety disorders and may be a pot entially useful compound to test against seizures, ischemia, mania, and str oke. (C) 2001 Wiley-Liss, Inc.