Table of Contents
ISRN Pharmacology
Volume 2012 (2012), Article ID 427267, 9 pages
http://dx.doi.org/10.5402/2012/427267
Review Article

Beyond Dopamine: Glutamate as a Target for Future Antipsychotics

1Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London SE5 8AF, UK
2North East London NHS Foundation Trust, Ilford IG3 8XJ, UK
3Cognition, Schizophrenia and Imaging Laboratory, Department of Psychological Medicine, Institute of Psychiatry, King’s College London, London SE5 8AF, UK
4Oxleas NHS Foundation Trust, Princess Royal University Hospital, Orpington BR6 8NY, UK

Received 29 April 2012; Accepted 6 June 2012

Academic Editors: R. Fantozzi, H. Y. Lane, P. Olinga, and K. Tamura

Copyright © 2012 Kyra-Verena Sendt et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The dopamine hypothesis of schizophrenia remains the primary theoretical framework for the pharmacological treatment of the disorder. Despite various lines of evidence of dopaminergic abnormalities and reasonable efficacy of current antipsychotic medication, a significant proportion of patients show suboptimal treatment responses, poor tolerability, and a subsequent lack of treatment concordance. In recent decades, intriguing evidence for the critical involvement of other neurotransmitter systems in the pathophysiology of schizophrenia has emerged, most notably of dysfunctions within the glutamate pathways. Consequently, the glutamate synapse has arisen as a promising target for urgently needed novel antipsychotic compounds—particularly in regards to debilitating negative and cognitive symptoms poorly controlled by currently available drugs. In this paper, recent findings integrating glutamatergic and dopaminergic abnormalities in schizophrenia and their implications for novel pharmacological targets are discussed. An overview of compounds in various stages of development is given: drugs enhancing NMDA receptor function as well as metabotropic glutamate receptor (mGluR) agonist and positive allosteric modulators (PAMs) are emphasised. Together with other agents more indirectly affecting glutamatergic neurotransmission, their potential future role in the pharmacotherapy of schizophrenia is critically evaluated.