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.
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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 |
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