Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity

Drug Discov Today. 2016 Mar;21(3):454-64. doi: 10.1016/j.drudis.2016.01.016. Epub 2016 Feb 6.

Abstract

Major depression is a chronic and debilitating illness that effects approximately 1 in 5 people, but currently available treatments are limited by low rates of efficacy, therapeutic time lag, and undesirable side effects. Recent efforts have been directed towards investigating rapid-acting agents that reverse the behavioral and neuronal deficits of chronic stress and depression, notably the glutamate NMDA receptor antagonist ketamine. The cellular mechanisms underlying the rapid antidepressant actions of ketamine and related agents are discussed, as well as novel, selective glutamatergic receptor targets that are safer and have fewer side effects.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / therapeutic use*
  • Depression / drug therapy*
  • Depression / metabolism
  • Depression / physiopathology
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / physiopathology
  • Excitatory Amino Acid Agents / therapeutic use
  • GABA-A Receptor Agonists / therapeutic use
  • Glutamic Acid
  • Humans
  • Ketamine / therapeutic use
  • Muscarinic Antagonists / therapeutic use
  • Neuronal Plasticity
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Scopolamine / therapeutic use
  • Stress, Psychological / drug therapy
  • Stress, Psychological / physiopathology

Substances

  • Antidepressive Agents
  • Excitatory Amino Acid Agents
  • GABA-A Receptor Agonists
  • Muscarinic Antagonists
  • NR2B NMDA receptor
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Ketamine
  • Scopolamine