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Glutamatergic NMDA Receptor as Therapeutic Target for Depression

Adv Protein Chem Struct Biol. 2016:103:169-202. doi: 10.1016/bs.apcsb.2015.10.003. Epub 2015 Dec 17.

Abstract

Major depressive disorder (MDD) affects approximately 121 million individuals globally and poses a significant burden to the healthcare system. Around 50-60% of patients with MDD respond adequately to existing treatments that are primarily based on a monoaminergic system. However, the neurobiology of MDD has not been fully elucidated; therefore, it is possible that other biochemical alterations are involved. The glutamatergic system and its associated receptors have been implicated in the pathophysiology of MDD. In fact, the N-methyl-d-aspartate (NMDA) receptor, a glutamate receptor, is a binding or modulation site for both classical antidepressants and new fast-acting antidepressants. Thus, this review aims to present evidence describing the effect of antidepressants that modulate NMDA receptors and the mechanisms that contribute to the antidepressant response.

Keywords: Antidepressants; Ketamine; Major depressive disorder; NMDA receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidepressive Agents / metabolism*
  • Antidepressive Agents / therapeutic use
  • Ascorbic Acid / metabolism
  • Ascorbic Acid / therapeutic use
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / metabolism*
  • Depressive Disorder, Major / pathology
  • Glutamates / metabolism*
  • Glycine Agents / therapeutic use
  • Guanosine / metabolism
  • Humans
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Antidepressive Agents
  • Glutamates
  • Glycine Agents
  • Receptors, N-Methyl-D-Aspartate
  • Guanosine
  • Ascorbic Acid