Targeting glutamate synapses in schizophrenia.

Field JR, Walker AG, Conn PJ
Trends Mol Med. 2011 17 (12): 689-98

PMID: 21955406 · PMCID: PMC3225651 · DOI:10.1016/j.molmed.2011.08.004

Although early clinical observations implicated dopamine dysfunction in the neuropathology of schizophrenia, accumulating evidence suggests that multiple neurotransmitter pathways are dysregulated. The psychotomimetic actions of NMDA receptor antagonists point to an imbalance of glutamatergic signaling. Encouragingly, numerous preclinical and clinical studies have elucidated several potential targets for increasing NMDA receptor function and equilibrating glutamatergic tone, including the metabotropic glutamate receptors 2, 3 and 5, the muscarinic acetylcholine receptors M(1) and M(4), and the glycine transporter GlyT1. Highly specific allosteric and orthosteric ligands have been developed that modify the activity of these novel target proteins, and in this review we summarize both the glutamatergic mechanisms and the novel compounds that are increasing the promise for a multifaceted pharmacological approach to treat schizophrenia.

Copyright © 2011 Elsevier Ltd. All rights reserved.

MeSH Terms (16)

Animals Antipsychotic Agents Excitatory Amino Acid Agonists Glycine Plasma Membrane Transport Proteins Humans Ligands Mice Mice, Knockout Muscarinic Agonists Rats Receptors, Metabotropic Glutamate Receptors, Muscarinic Receptors, N-Methyl-D-Aspartate Schizophrenia Synapses Synaptic Transmission

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