Glutamate in CNS disorders as a target for drug development: an update

Abstract

The authors provide an extensive review of new data related to the role of glutamate in CNS disorders, describing new aspects in glutamate and glutamatergic receptors-NMDA receptors, NR2B-selective antagonists, non-NMDA ionotropic glutamate receptors, N-acetylaspartylglutamate, and glutamate and glycine transporters. New findings in animal models and in human diseases-stroke, traumatic brain injury, Alzheimer's, Parkinson's and Huntington's diseases, tardive dyskinesia, ALS, olivopontcerebellar degeneration, AIDS, allergic encephalomyelitis, epilepsy, anxiety, depression, schizophrenia, liver disease, aminoglycoside antibiotic-induced hearing loss, hemiplegia, chronic pain and drug tolerance and abuse-are presented. Finally, the authors cite the progress achieved in the development of agents that interact with the glutamatergic system: NMDA channel blockers, competitive NMDA receptor antagonists, NR2B-selective antagonists, glutamate release inhibitors, glycineB antagonists, AMPA and kainate receptor antagonists, AMPA receptor-positive modulators and agents that act by modifying endogenous kynurenic acid metabolism.