Possible Interaction: Gamma-Aminobutyric Acid and Phenelzine

“ Phenelzine also elevates brain GABA levels, and as yet unidentified metabolites of phenelzine may be responsible for this effect.”

“ Phenelzine also elevates brain GABA levels, and as yet unidentified metabolites of phenelzine may be responsible for this effect.”

“ PLZ has been shown to restore central nervous system (CNS) tissue concentrations of GABA and the monoamines (5-HT, NA) in EAE.”

“… phenelzine or PEH to rats has been … in rat brain levels of GABA and alanine while reducing levels of glutamine; these effects are abolished for phenelzine, but not for PEH, when … with another MAO inhibitor, suggesting that they are mediated by the MAO-catalyzed formation of PEH from phenelzine.”

“Both PEH isomers and phenelzine produced marked increases in rat brain levels of GABA and alanine while decreasing brain levels of glutamine.”

“Furthernore, the effective dose of phenelzine (15 mg/kg) administered to rats was associated with more than a 2-fold increase in whole brain levels of γ-aminobutyric acid (GABA), whereas an ineffective dose of phenelzine (5.1 mg/kg) did not significantly change GABA levels.”

“ Beta-Phenylethylidenehydrazine (PEH) has been demonstrated previously to be an inhibitor of gamma-aminobutyric acid transaminase (GABA-T) and to cause a marked increase in rat brain levels of GABA, a major neurotransmitter.”

“Acute and chronic PLZ administration increase brain GABA levels, an effect due, at least in part, to an inhibition of the activity of the GABA metabolizing enzyme, GABA transaminase (GABA-T).2.”

“Acetylation of phenelzine at the N2 position presumably interferes with the inhibition of the transaminase enzymes for γ-aminobutyric acid and alanine.”

“Interestingly, PLZ also elevates brain levels of gamma-aminobutyric acid (GABA), and previous studies have suggested that these increases may also contribute to the anxiolytic effects of PLZ.”

“These findings provide further evidence that GABA may play an important role in the actions of PLZ and suggest that PEH should be pursued further as a GABAergic drug in its own right.”

“Using in vivo microdialysis in conscious, freely moving rats, combined with high performance liquid chromatography, the present experiments determined that PLZ (15 or 30 mg/kg, free base weight) increases extracellular levels of GABA in the caudate-putamen and nucleus accumbens.”