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Related Experiment Video

Updated: Mar 6, 2026

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Targeting glutamate signalling in depression: progress and prospects.

James W Murrough1, Chadi G Abdallah2, Sanjay J Mathew3

  • 1Mood and Anxiety Disorders Program, Department of Psychiatry; Fishberg Department of Neuroscience; and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

Nature Reviews. Drug Discovery
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Summary

Ketamine, a glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist, shows rapid antidepressant effects, driving research into new glutamate-signalling modulators for major depressive disorder (MDD). Further studies are needed to address safety, efficacy, and mechanisms for these novel depression treatments.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Psychiatry

Background:

  • Major depressive disorder (MDD) presents a significant global health burden with limited treatment efficacy.
  • Ketamine, a glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist, has emerged as a rapidly acting antidepressant, stimulating interest in glutamate pathway modulation.

Purpose of the Study:

  • To review the progress in developing glutamate-signalling modulators for depression treatment.
  • To examine preclinical and translational studies on the mechanisms of action of glutamate-targeting antidepressants.

Main Methods:

  • Literature review of recent preclinical and translational studies.
  • Analysis of the development of glutamate-signalling modulators for antidepressant therapies.

Main Results:

  • Ketamine's repurposing has accelerated research into novel glutamate-based antidepressants.
  • Significant progress has been made in understanding the mechanisms of action for these agents.

Conclusions:

  • Glutamate-targeting drugs represent a promising avenue for novel depression treatments.
  • Further research is essential to address safety, efficacy, dose-response, and therapeutic mechanisms for widespread clinical application.