Abstract
Background: A growing body of evidence suggests that glutamatergic system, especially the abnormalities of glutamate and N-methyl-D-aspartate (NMDA) receptors contribute to the pathophysiology of major depressive disorders. An imbalance in glutamatergic neurotransmission may contribute to increased levels of NMDA agonism, thereby enhancing excitatory activity in most brain circuits involved in major depression. Although NMDA receptor antagonists have been demonstrated to possess antidepressant-like activity, the molecular changes underlying abnormal glutamatergic signaling still remain poorly understood. Therefore, we aimed to review the current literature focusing on the main pharmacological properties and the impact of glutamatergic drugs targeting NMDA receptors in major depression. Methods: A detailed literature search in PubMed/Medline and ScienceDirect databases using the terms glutamate, depression and major depressive disorder has been performed. Results: Most drugs acting at glutamatergic receptors showed biochemical effects indicative of antidepressant activity in both clinical and preclinical studies. Recent neuroimaging and genetic contributions also confirm the antidepressant properties of these medications. However, human studies including NMDA receptor antagonists provided mixed results. In overall, glutamatergic receptor modulation may facilitate neuronal stem cell enhancement (neurogenesis) as well as the release of neurotransmitters associated with treatment response to depression in humans. Limitations: Cognitive side effects and psychotomimetic properties complicate the application and the development of clinically useful agents. Conclusions: Glutamatergic system represents a target for effective intervention in major depression. Specifically, those glutamatergic medications targeting NMDA receptors by inhibiting the release of neurotransmitters or modulating its post-synaptic responses may serve as molecule modulators with specific antidepressant properties.
Keywords: Glutamatergic abnormalities, NMDA receptors, major depression, antidepressant drugs
Current Pharmaceutical Design
Title:Pharmacological Properties of Glutamatergic Drugs Targeting NMDA Receptors and their Application in Major Depression
Volume: 19 Issue: 10
Author(s): Gianluca Serafini, Maurizio Pompili, Marco Innamorati, Yogesh Dwivedi, Goutam Brahmachari and Paolo Girardi
Affiliation:
Keywords: Glutamatergic abnormalities, NMDA receptors, major depression, antidepressant drugs
Abstract: Background: A growing body of evidence suggests that glutamatergic system, especially the abnormalities of glutamate and N-methyl-D-aspartate (NMDA) receptors contribute to the pathophysiology of major depressive disorders. An imbalance in glutamatergic neurotransmission may contribute to increased levels of NMDA agonism, thereby enhancing excitatory activity in most brain circuits involved in major depression. Although NMDA receptor antagonists have been demonstrated to possess antidepressant-like activity, the molecular changes underlying abnormal glutamatergic signaling still remain poorly understood. Therefore, we aimed to review the current literature focusing on the main pharmacological properties and the impact of glutamatergic drugs targeting NMDA receptors in major depression. Methods: A detailed literature search in PubMed/Medline and ScienceDirect databases using the terms glutamate, depression and major depressive disorder has been performed. Results: Most drugs acting at glutamatergic receptors showed biochemical effects indicative of antidepressant activity in both clinical and preclinical studies. Recent neuroimaging and genetic contributions also confirm the antidepressant properties of these medications. However, human studies including NMDA receptor antagonists provided mixed results. In overall, glutamatergic receptor modulation may facilitate neuronal stem cell enhancement (neurogenesis) as well as the release of neurotransmitters associated with treatment response to depression in humans. Limitations: Cognitive side effects and psychotomimetic properties complicate the application and the development of clinically useful agents. Conclusions: Glutamatergic system represents a target for effective intervention in major depression. Specifically, those glutamatergic medications targeting NMDA receptors by inhibiting the release of neurotransmitters or modulating its post-synaptic responses may serve as molecule modulators with specific antidepressant properties.
Export Options
About this article
Cite this article as:
Serafini Gianluca, Pompili Maurizio, Innamorati Marco, Dwivedi Yogesh, Brahmachari Goutam and Girardi Paolo, Pharmacological Properties of Glutamatergic Drugs Targeting NMDA Receptors and their Application in Major Depression, Current Pharmaceutical Design 2013; 19 (10) . https://dx.doi.org/10.2174/13816128113199990293
DOI https://dx.doi.org/10.2174/13816128113199990293 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Cannabis Associated “High” Cardiovascular Morbidity and Mortality: Marijuana Smoke Like Tobacco Smoke? A Déjà Vu/Déjà Vécu Story?
Mini-Reviews in Medicinal Chemistry Tau Phosphorylation and Aggregation as a Therapeutic Target in Tauopathies
CNS & Neurological Disorders - Drug Targets A Validation and Estimation of Total Eicosapentaenoic and Docosahexaenoic acids Using LC-MS/MS with Rapid Hydrolysis Enzymatic Method for Hydrolysis of Omega Lipids in Human Plasma and its Application in the Pharmacokinetic Study
Current Pharmaceutical Analysis Review and Research Analysis of Computational Target Methods Using BioRuby and In silico Screening of Herbal Lead Compounds Against Pancreatic Cancer Using R Programming
Current Drug Metabolism New Trends in the Development of Positive Allosteric Modulators of AMPA Receptors
Current Medicinal Chemistry - Central Nervous System Agents Gastrodia Elata Bl Attenuates Cocaine-Induced Conditioned Place Preference and Convulsion, but not Behavioral Sensitization in Mice: Importance of GABAA Receptors
Current Neuropharmacology The Positive Synergism of CPT and MK-801 in Behavioral Tests and in Reduction of Environmental Stress and Redox Signaling Changes in Mice Cerebral Cortex
CNS & Neurological Disorders - Drug Targets Opiate-Induced Analgesia: Contributions From Mu, Delta and Kappa Opioid Receptors Mouse Mutants
Current Pharmaceutical Design Inquiries into the Biological Significance of Transmembrane AMPA Receptor Regulatory Protein (TARP) γ−8 Through Investigations of TARP γ−8 Null Mice§
CNS & Neurological Disorders - Drug Targets Neuroprotective Effects of Lutein in the Retina
Current Pharmaceutical Design Optimization of Antidepressant Use with Pharmacogenetic Strategies
Current Genomics Development of Xanthine Based Inhibitors Targeting Phosphodiesterase 9A
Letters in Drug Design & Discovery Clinical Application of the Vestibular Stimulation Effect on Balance Disorders with Dementia
Current Alzheimer Research Direct Analysis of Methadone in Exhaled Breath Condensate by Capillary Zone Electrophoresis
Current Pharmaceutical Analysis Folic Acid Can Contribute to Memory Deficit and Na+, K+- ATPase Failure in the Hippocampus of Adolescent Rats Submitted to Hypoxia- Ischemia
CNS & Neurological Disorders - Drug Targets Gonadotropin-Releasing Hormone Receptor System: Modulatory Role in Aging and Neurodegeneration
CNS & Neurological Disorders - Drug Targets Editorial [Hot Topic: Progressive and Unconventional Pharmacotherapeutic Approaches to Alzheimers Disease Therapy (Guest Editors: Stuart Maudsley & Wayne Chadwick)]
Current Alzheimer Research Prevalence of Frailty in Mild to Moderate Alzheimer's Disease: A Systematic Review and Meta-analysis
Current Alzheimer Research Prospect of a Dopamine Contribution in the Next Generation of Antidepressant Drugs: The Triple Reuptake Inhibitors
Current Drug Targets Variability in the Effects of Nicotine on Different Regions of the Brain: Changes in the Concentration of Superoxide Dismutase Isoforms
Central Nervous System Agents in Medicinal Chemistry