Glutamate- and GABA-based CNS therapeutics

Curr Opin Pharmacol. 2006 Feb;6(1):7-17. doi: 10.1016/j.coph.2005.11.005. Epub 2005 Dec 22.


Glutamate- and GABA-releasing neurons form the basis for neurotransmission in the mammalian central nervous system (CNS). The co-ordination of these excitatory and inhibitory systems, together with intrinsic voltage-gated ion channels and G-protein-coupled receptor modulation, provides the diverse neuronal firing patterns, network activity and synaptic plasticity that are required for the complexity of CNS function. Virtually all of the known molecular components of the gamma-aminobutyric acid (GABA) and glutamate neurotransmitter systems have been considered as potential therapeutic targets. Positive allosteric modulators of GABAA receptors, such as the benzodiazepines, have found wide clinical use, and the N-methyl-D-aspartate receptor antagonists ketamine and memantine have therapeutic utility. In these fundamental neurotransmitter systems, drugs that provide allosteric modulation of ligand-gated ion channels or G-protein-coupled receptors, or seek to selectively target receptor subtypes, appear to hold the greatest promise for the desired balance of efficacy and tolerability. This might also be achieved through targeting transporter subtypes. A large number of compounds based on these strategies are currently in clinical trials for diseases that span a wide range of CNS disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Clinical Trials as Topic
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Agonists / therapeutic use
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Excitatory Amino Acid Antagonists / therapeutic use
  • GABA Agonists / pharmacology*
  • GABA Agonists / therapeutic use
  • GABA Antagonists / pharmacology*
  • GABA Antagonists / therapeutic use
  • Glutamic Acid / metabolism
  • Humans
  • Neurons / drug effects
  • Neurons / metabolism
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / metabolism
  • Receptors, GABA / drug effects
  • Receptors, GABA / metabolism
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • GABA Agonists
  • GABA Antagonists
  • Receptors, AMPA
  • Receptors, GABA
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • gamma-Aminobutyric Acid