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European Archives of Psychiatry and Clinical Neuroscience

Erschienen in:

01.08.2013 | Invited Review

Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders

verfasst von: Kenji Hashimoto, Berend Malchow, Peter Falkai, Andrea Schmitt

Erschienen in: European Archives of Psychiatry and Clinical Neuroscience | Ausgabe 5/2013

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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.

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Titel: Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders
verfasst von: Kenji Hashimoto
Berend Malchow
Peter Falkai
Andrea Schmitt
Publikationsdatum: 01.08.2013
Verlag: Springer Berlin Heidelberg
Erschienen in: European Archives of Psychiatry and Clinical Neuroscience / Ausgabe 5/2013
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-013-0399-y

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Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders

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