Depression and schizophrenia viewed from the perspective of amino acidergic neurotransmission: Antipodes of psychiatric disorders

Pharmacol Ther. 2019 Jan:193:75-82. doi: 10.1016/j.pharmthera.2018.08.010. Epub 2018 Aug 25.

Abstract

Depression and schizophrenia are burdensome, costly serious and disabling mental disorders. Moreover the existing treatments are not satisfactory. As amino-acidergic (AA) neurotransmitters built a vast majority of brain neurons, in this article we plan to focus on drugs influencing AA neurotransmission in both diseases: we will discuss several facts concerning glutamatergic and GABA-ergic neurotransmission in these diseases, based mainly on preclinical experiments that used stimulators and/or blockers of both neurotransmitter systems. In general a picture emerges showing, that treatments that increase excitatory effects (with either antagonists or agonists) tend to evoke antidepressant effects, while treatments that increase inhibitory effects tend to display antipsychotic properties. Moreover, it seems that the antidepressant activity of a given compound excludes it as a potential antipsychotic and vice versa.

Keywords: Agonists/positive allosteric modulators; Antagonists/negative allosteric modulators; Depression; GABA; Glutamate; Schizophrenia.

Publication types

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

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Depression / drug therapy*
  • Depression / metabolism
  • Glutamic Acid / metabolism*
  • Humans
  • Receptors, GABA / metabolism
  • Receptors, Ionotropic Glutamate / metabolism
  • Receptors, Metabotropic Glutamate / metabolism
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism
  • Synaptic Transmission
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Antipsychotic Agents
  • Receptors, GABA
  • Receptors, Ionotropic Glutamate
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid
  • gamma-Aminobutyric Acid