Cited by 530Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchTreatment of Major Depression

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

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Krystal, John H., D'Souza, D. Cyril, Mathalon, Daniel, Perry, Edward, Belger, Aysenil, Hoffman, Ralph·2003·Psychopharmacology

DOI 10.1007/s00213-003-1582-z

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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.

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Authors: Krystal, J. H., D'Souza, D. C., Mathalon, D., Perry, E., Belger, A., & Hoffman, R.
Affiliations: VA Connecticut Healthcare System (US)
Yale University (US)
Yale New Haven Hospital (US)
Corresponding author: Krystal, John H.
ORCID: Krystal, John H.
Mathalon, Daniel
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2003-09-01
Volume: 169
Issue: 3-4
Pages: 215-233
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-003-1582-z
OpenAlex: W2020140782
Cited by: 530
References: 307
Citations by year: 2026: 11 · 2025: 10 · 2024: 11 · 2023: 16 · 2022: 11 · 2021: 15 · 2020: 20 · 2019: 19 · 2018: 24 · 2017: 27 · 2016: 28 · 2015: 28 · 2014: 20 · 2013: 33 · 2012: 40
FWCI: 11.05
Type: journal article
Language: en
Open access: green
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Newcastle University ePrints (Newcastle Univesity)
Funders: National Institutes of Health (5k02aa000261-04)
National Institute on Alcohol Abuse and Alcoholism (K02 AA 00261-01)
National Institute of Mental Health (5P50 MH44866-12, P50MH044866)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: schizophrenia, NMDA receptor antagonists, ketamine, glutamatergic function, cortical connectivity, disinhibition, schizophrenia pharmacotherapy, cognitive impairment, translational neuroscience, antipsychotic drug development
MeSH terms: Animals, Cerebral Cortex, Cognition, Humans, Ketamine, Models, Neurological, Neural Pathways, Schizophrenia, Antipsychotic Agents, Receptors, N-Methyl-D-Aspartate, Excitatory Amino Acid Antagonists, Glutamic Acid

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

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