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

  • K. F. McKenna
  • D. J. McManus
  • G. B. Baker
  • R. T. Coutts
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 41)

Summary

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 γ-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 hydra-zine 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.

Keywords

Glutamic Acid Decarboxylase Gaba Level Brain Gaba GABAergic Function Brain Gaba Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • K. F. McKenna
    • 1
  • D. J. McManus
    • 1
  • G. B. Baker
    • 1
    • 2
  • R. T. Coutts
    • 1
    • 2
  1. 1.Neurochemical Research Unit, Department of PsychiatryUniversity of AlbertaEdmontonCanada
  2. 2.Neurochemical Research Unit, Faculty of Pharmacy and Pharmaceutical SciencesUniversity of AlbertaEdmontonCanada

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