Effects of the antidepressant/antipanic drug phenelzine and its putative metabolite phenylethylidenehydrazine on extracellular γ-aminobutyric acid levels in the striatum11Abbreviations: DA, dopamine; GABA, γ-aminobutyric acid; GABA-T, GABA transaminase; 5-HT, 5-hydroxytryptamine or serotonin; MAO, monoamine oxidase; N2-acetylPLZ, N2-acetylphenelzine; NE, norepinephrine; PEH, phenylethylidenehydrazine; and PLZ, phenelzine, 2-phenylethylhydrazine
التفاصيل البيبلوغرافية
العنوان:
Effects of the antidepressant/antipanic drug phenelzine and its putative metabolite phenylethylidenehydrazine on extracellular γ-aminobutyric acid levels in the striatum11Abbreviations: DA, dopamine; GABA, γ-aminobutyric acid; GABA-T, GABA transaminase; 5-HT, 5-hydroxytryptamine or serotonin; MAO, monoamine oxidase; N2-acetylPLZ, N2-acetylphenelzine; NE, norepinephrine; PEH, phenylethylidenehydrazine; and PLZ, phenelzine, 2-phenylethylhydrazine
Phenelzine (PLZ) is a non-selective monoamine oxidase inhibitor (MAOI) commonly used to treat depression and panic disorder. As expected, PLZ increases brain levels of dopamine, norepinephrine, and serotonin. Interestingly, PLZ also elevates brain levels of γ-aminobutyric acid (GABA), and previous studies have suggested that these increases may also contribute to the anxiolytic effects of PLZ. 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. The results also indicated that phenylethylidenehydrazine (PEH; 29.6 mg/kg, free base weight), a putative intermediate metabolite of PLZ that is not an MAOI, also significantly increases extracellular GABA levels in the caudate-putamen. 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.
