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NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development

Lookup NU author(s): Emeritus Professor Elaine Perry

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Abstract

There is an urgent need to improve the pharmacotherapy of schizophrenia despite the introduction of important new medications. New treatment insights may come from appreciating the therapeutic implications of model psychoses. In particular, basic and clinical studies have employed the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, ketamine, as a probe of NMDA receptor contributions to cognition and behavior. These studies illustrate a translational neuroscience approach for probing mechanistic hypotheses related to the neurobiology and treatment of schizophrenia and other disorders. Two particular pathophysiologic themes associated with schizophrenia, the disturbance of cortical connectivity and the disinhibition of glutamatergic activity may be modeled by the administration of NMDA receptor antagonists. The purpose of this review is to consider the possibility that agents that attenuate these two components of NMDA receptor antagonist response may play complementary roles in the treatment of schizophrenia.


Publication metadata

Author(s): Perry E; Krystal JH; D'Souza DC; Mathalon D; Belger A; Hoffman R

Publication type: Article

Publication status: Published

Journal: Psychopharmacology

Year: 2003

Volume: 169

Issue: 3-4

Pages: 215-233

ISSN (print): 0033-3158

ISSN (electronic): 1432-2072

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00213-003-1582-z

DOI: 10.1007/s00213-003-1582-z

Notes: Journal Article Review


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