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β‐phenylethylidenehydrazine, a novel inhibitor of GABA transaminase
Author(s) -
Paslawski T.,
Knaus E.,
Iqbal N.,
Coutts R.T.,
Baker G.B.
Publication year - 2001
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.1202
Subject(s) - gaba transaminase , phenelzine , monoamine oxidase , clorgyline , pharmacology , chemistry , antidepressant , neurotransmitter , metabolite , tetrabenazine , endocrinology , medicine , biochemistry , dopamine , enzyme , receptor , hippocampus , glutamate decarboxylase
Abstract Phenylethylidenehydrazine (PEH), a proposed metabolite of phenelzine (PLZ), was synthesized in our laboratories and administered to rats in a series of 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 (γ‐aminobutyric acid (GABA). Like PLZ, PEH inhibited GABA transaminase (GABA‐T) and caused marked, long‐lasting increases in rat brain levels of GABA. The addition of the double bond in PEH caused a marked decrease in its ability to inhibit MAO 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 potentially useful compound to test against seizures, ischemia, mania, and stroke. Drug Dev. Res. 54:35–39, 2001. © 2001 Wiley‐Liss, Inc.