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Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders.

Abstract：

:Severe psychiatric disorders such as schizophrenia are related to cognitive and negative symptoms, which often are resistant to current treatment approaches. The glutamatergic system has been implicated in the pathophysiology of schizophrenia and affective disorders. A key component is the dysfunction of the glutamatergic N-methyl-D-aspartate (NMDA) receptor. Substances regulating activation/inhibition of the NMDA receptor have been investigated in schizophrenia and major depression and are promising in therapeutic approaches of negative symptoms, cognition, and mood. In schizophrenia, add-on treatments with glycine, D-serine, D-alanine, D-cycloserine, D-amino acid oxidase inhibitors, glycine transporter-1 (GlyT-1) inhibitors (e.g., sarcosine, bitopertin) and agonists (e.g., LY2140023) or positive allosteric modulator (e.g., ADX71149) of group II metabotropic glutamate receptors (mGluRs) have been studied. In major depression, the NMDA receptor antagonists (e.g., ketamine, AZD6765), GluN2B subtype antagonists (e.g., traxoprodil, MK-0657), and partial agonists (e.g., D-cycloserine, GLYX-13) at the glycine site of the NMDA receptor have been proven to be effective in animal studies and first clinical trials. In addition, clinical studies of mGluR2/3 antagonist BCI-838 (a prodrug of BCI-632 (MGS0039)), mGluR2/3-negative allosteric modulators (NMAs) (e.g., RO499819, RO4432717), and mGluR5 NAMs (e.g., AZD2066, RO4917523) are in progress. Future investigations should include effects on brain structure and activation to elucidate neural mechanisms underlying efficacy of these drugs.

journal_name

Eur Arch Psychiatry Clin Neurosci

journal_title

European archives of psychiatry and clinical neuroscience

authors

Hashimoto K,Malchow B,Falkai P,Schmitt A

doi

10.1007/s00406-013-0399-y

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

367-77

issue

5

eissn

0940-1334

issn

1433-8491

journal_volume

263

pub_type

杂志文章,评审

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