Glutamatergic dysregulation in mood disorders: opportunities for the discovery of novel drug targets

Expert Opin Ther Targets. 2020 Dec;24(12):1187-1209. doi: 10.1080/14728222.2020.1836160. Epub 2020 Nov 3.

Abstract

Introduction: Recently, a considerable attention has been paid to glutamatergic conception of mood disorders. The development of new treatment strategies targeted at glutamate provides new opportunities for the treatment of mood disorders. It is expected that these novel therapeutic options will provide a fast and sustained antidepressant effect and will be better tolerated by patients than the currently available antidepressants.

Areas covered: This paper discusses glutamatergic abnormalities in mood disorders and reviews novel glutamate-based drugs developed for the treatment of these disorders. We have searched the PubMed and EMBASE databases, presented the results of relevant clinical studies and also describe novel glutamate-based agents that are under investigation.

Expert opinion: The glutamatergic system plays many important roles in energy metabolism of the brain and neurotransmission; therefore, any attempt to identify novel therapeutic targets within this system seems justified. The effective development of new glutamate-based drugs requires, among others, a more in-depth exploration and understanding of the anatomy, function, and localization of different glutamatergic receptors in the brain. In our opinion, novel glutamate-based antidepressants will find application in the treatment of mood disorders and present an option will be widely used in clinical practice in the future.

Keywords: Depression; NMDA; antidepressant; glutamate; glutamatergic system; mood disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Brain / metabolism
  • Brain / physiopathology
  • Drug Development
  • Glutamic Acid / metabolism*
  • Humans
  • Molecular Targeted Therapy*
  • Mood Disorders / drug therapy*
  • Mood Disorders / physiopathology
  • Receptors, Glutamate / metabolism

Substances

  • Antidepressive Agents
  • Receptors, Glutamate
  • Glutamic Acid