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Updated: Aug 15, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments
J H Krystal1, G Sanacora, H Blumberg
1Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. john.krystal@yale.edu
Abstract:
Glutamate and gamma-amino butyric acid (GABA) systems are emerging as targets for development of medications for mood disorders. There is increasing preclinical and clinical evidence that antidepressant drugs directly or indirectly reduce N-methyl-D-aspartate glutamate receptor function. Drugs that reduce glutamatergic activity or glutamate receptor-related signal transduction may also have antimanic effects. Recent studies employing magnetic resonance spectroscopy also suggest that unipolar, but not bipolar, depression is associated with reductions in cortical GABA levels. Antidepressant and mood-stabilizing treatments also appear to raise cortical GABA levels and to ameliorate GABA deficits in patients with mood disorders. The preponderance of available evidence suggests that glutamatergic and GABAergic modulation may be an important property of available antidepressant and mood-stabilizing agents. Future research will be needed to develop and evaluate new agents with specific glutamate and GABA receptor targets in the treatment of mood disorders.
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