Abstract
Ample evidence indicates that glutamate homeostasis and neurotransmission are disrupted in major depressive disorder; but the nature of this disruption and the mechanisms by which it contributes to the syndrome are unclear. Likewise, the effect of existing antidepressants on glutamate is unclear, as is the potential of drugs directly targeting glutamatergic neurotransmission to act as novel antidepressant medications. These are areas of active research. Here we review current knowledge of the contribution of the NMDA receptor, one of the several types of glutamate receptor, to depression and its treatment. Several lines of evidence, in humans and in animal models, support the contention that neurotransmission via the NMDA receptor is dysregulated in depression. Drugs that target the NMDA receptor have shown antidepressant properties in both clinical and preclinical studies. Nevertheless, other effects of such medications, including both cognitive side effects and their psychotomimetic properties, complicate such an application and represent a challenge to the development of clinically useful agents.
Keywords: Metabotropic glutamate receptors, NR2A subunit gene, Ketamine, NMDA blockade, EAAT2 glutamate transporters
CNS & Neurological Disorders - Drug Targets
Title: The NMDA Receptor as a Therapeutic Target in Major Depressive Disorder
Volume: 6 Issue: 2
Author(s): Christopher Pittenger, Gerard Sanacora and John H. Krystal
Affiliation:
Keywords: Metabotropic glutamate receptors, NR2A subunit gene, Ketamine, NMDA blockade, EAAT2 glutamate transporters
Abstract: Ample evidence indicates that glutamate homeostasis and neurotransmission are disrupted in major depressive disorder; but the nature of this disruption and the mechanisms by which it contributes to the syndrome are unclear. Likewise, the effect of existing antidepressants on glutamate is unclear, as is the potential of drugs directly targeting glutamatergic neurotransmission to act as novel antidepressant medications. These are areas of active research. Here we review current knowledge of the contribution of the NMDA receptor, one of the several types of glutamate receptor, to depression and its treatment. Several lines of evidence, in humans and in animal models, support the contention that neurotransmission via the NMDA receptor is dysregulated in depression. Drugs that target the NMDA receptor have shown antidepressant properties in both clinical and preclinical studies. Nevertheless, other effects of such medications, including both cognitive side effects and their psychotomimetic properties, complicate such an application and represent a challenge to the development of clinically useful agents.
Export Options
About this article
Cite this article as:
Pittenger Christopher, Sanacora Gerard and Krystal H. John, The NMDA Receptor as a Therapeutic Target in Major Depressive Disorder, CNS & Neurological Disorders - Drug Targets 2007; 6 (2) . https://dx.doi.org/10.2174/187152707780363267
DOI https://dx.doi.org/10.2174/187152707780363267 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Pathologically-Activated Therapeutics for Neuroprotection: Mechanism of NMDA Receptor Block by Memantine and S-Nitrosylation
Current Drug Targets RNA Interference as A Gene-Specific Approach for Molecular Medicine
Current Medicinal Chemistry Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration
Current Neuropharmacology Myelin Sheaths and Autoimmune Response Induced by Myelin Proteins and Alphaviruses. I. Physicochemical Background
Current Medicinal Chemistry Mitochondrial Permeability Transition Pore as a Suitable Targ e t for Neuroprotective Agents Against Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets Protein Homeostasis as a Therapeutic Target for Diseases of Protein Conformation
Current Topics in Medicinal Chemistry Stem Cell Therapies for the Lysosomal Storage Diseases – the Quintessential Neurodegenerative Diseases
Current Stem Cell Research & Therapy Reversal of Bone Cancer Pain by HSV-1-Mediated Silencing of CNTF in an Afferent Area of the Spinal Cord Associated with AKT-ERK Signal Inhibition
Current Gene Therapy Recent Approaches for Studying the Role of Glia
CNS & Neurological Disorders - Drug Targets Ion Channels on Microglia: Therapeutic Targets for Neuroprotection
CNS & Neurological Disorders - Drug Targets Neurotrophic Factors for the Investigation and Treatment of Movement Disorders
Current Medicinal Chemistry - Central Nervous System Agents Overview of PCTK3/CDK18: A Cyclin-Dependent Kinase Involved in Specific Functions in Post-Mitotic Cells
Current Medicinal Chemistry Heat Shock Proteins and Ion Channels. Functional Interactions and Therapeutic Consequences
Current Pharmaceutical Biotechnology Stem Cells with Neurogenic Potential and Steroid Hormones
Current Topics in Medicinal Chemistry The Role of Mitochondrial Function in Glutamate-Dependent Metabolism in Neuronal Cells
Current Pharmaceutical Design Targeting Mitochondria in Fighting Cancer
Current Pharmaceutical Design MicroRNAs: Macro Challenges on Understanding Human Biological Functions and Neurological Diseases
Current Molecular Medicine Old Friends in New Constellations - the Hematopoetic Growth Factors G-CSF, GMCSF, and EPO for the Treatment of Neurological Diseases
Current Medicinal Chemistry CSF Ubiquitin As a Specific Biomarker in Alzheimer's Disease
Current Alzheimer Research Codon Usage Biases in Alzheimers Disease and Other Neurodegenerative Diseases
Protein & Peptide Letters