Chronic administration of the antidepressant phenelzine and its N-acetyl analogue: effects on GABAergic function.

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McKenna KF, McManus DJ, Baker GB, Coutts RT

Chronic administration of the antidepressant phenelzine and its N-acetyl analogue: effects on GABAergic function.

J Neural Transm Suppl. 1994;41:115-22.

PubMed ID

7931216 [ View in PubMed

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Abstract

The MAO inhibitor phenelzine (2-phenylethylhydrazine; PLZ) is used widely in psychiatry for the treatment of depression and panic disorder. Its N-acetyl metabolite, N2-acetylphenelzine (N2AcPLZ) is a reasonably potent nonselective inhibitor of monoamine oxidase (MAO) that causes elevation in brain levels of the biogenic amines. In the studies reported here, PLZ (0.05 mmol/kg/day), N2AcPLZ (0.10 mmol/kg/day) or vehicle were administered to male rats for 28 days s.c. with Alzet minipumps, and their effects on GABAergic function were examined. Whole brain concentrations of gamma-aminobutyric acid (GABA) were significantly elevated in the PLZ but not in the N2AcPLZ-treated group. PLZ was found to inhibit the anabolic enzyme glutamic acid decarboxylase (GAD) and, to a greater extent, the catabolic enzyme GABA transaminase (GABA-T). The results of these investigations suggest that the free hydrazine moiety in PLZ is crucial to producing the elevated levels of GABA, probably through inhibition of GABA-T. Despite the considerable increase in whole brain GABA levels in the PLZ-treated rats, there were no significant differences in GABAA or benzodiazepine receptor binding parameters (KD or Bmax) between the groups as measured using 3H-muscimol and 3H-flunitrazepam in radioligand binding assays.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Phenelzine	4-aminobutyrate aminotransferase, mitochondrial	Protein	Humans	Unknown	Inhibitor	Details
Phenelzine	Glutamic acid decarboxylase	Protein	Humans	Unknown	Inhibitor	Details