Novel glutamatergic drugs for the treatment of mood disorders

Kyle AB Lapidus, Laili Soleimani, James W MurroughMood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USAAbstract: Mood disorders are common and debilitating, resulting in a significant public health burden. Current treatments are only...

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Autores principales:	Murrough JW, Lapidus KAB, Soleimani L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/c642c0191b914f869c9fb57dce8d4303
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spelling	oai:doaj.org-article:c642c0191b914f869c9fb57dce8d43032021-12-02T07:49:09ZNovel glutamatergic drugs for the treatment of mood disorders1176-63281178-2021https://doaj.org/article/c642c0191b914f869c9fb57dce8d43032013-08-01T00:00:00Zhttp://www.dovepress.com/novel-glutamatergic-drugs-for-the-treatment-of-mood-disorders-a13927https://doaj.org/toc/1176-6328https://doaj.org/toc/1178-2021Kyle AB Lapidus, Laili Soleimani, James W MurroughMood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USAAbstract: Mood disorders are common and debilitating, resulting in a significant public health burden. Current treatments are only partly effective and patients who have failed to respond to trials of existing antidepressant agents (eg, those who suffer from treatment-resistant depression [TRD]) require innovative therapeutics with novel mechanisms of action. Although neuroscience research has elucidated important aspects of the basic mechanisms of antidepressant action, most antidepressant drugs target monoaminergic mechanisms identified decades ago. Glutamate, the major excitatory neurotransmitter in the central nervous system, and glutamatergic dysfunction has been implicated in mood disorders. These data provide a rationale for the pursuit of glutamatergic agents as novel therapeutic agents. Here, we review preclinical and clinical investigations of glutamatergic agents in mood disorders with a focus on depression. We begin with discussion of evidence for the rapid antidepressant effects of ketamine, followed by studies of the antidepressant efficacy of the currently marketed drugs riluzole and lamotrigine. Promising novel agents currently in development, including N-methyl-D-aspartate (NMDA) receptor modulators, 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) receptor modulators, and drugs with activity at the metabotropic glutamate (mGlu) receptors are then reviewed. Taken together, both preclinical and clinical evidence exists to support the pursuit of small molecule modulators of the glutamate system as novel therapeutic agents in mood disorders. It is hoped that by targeting neural systems outside of the monoamine system, more effective and perhaps faster acting therapeutics can be developed for patients suffering from these disabling disorders.Keywords: glutamate, mood disorders, major depressive disorder, ketamine, NMDA, AMPAMurrough JWLapidus KABSoleimani LDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2013, Iss default, Pp 1101-1112 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Murrough JW Lapidus KAB Soleimani L Novel glutamatergic drugs for the treatment of mood disorders
description	Kyle AB Lapidus, Laili Soleimani, James W MurroughMood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USAAbstract: Mood disorders are common and debilitating, resulting in a significant public health burden. Current treatments are only partly effective and patients who have failed to respond to trials of existing antidepressant agents (eg, those who suffer from treatment-resistant depression [TRD]) require innovative therapeutics with novel mechanisms of action. Although neuroscience research has elucidated important aspects of the basic mechanisms of antidepressant action, most antidepressant drugs target monoaminergic mechanisms identified decades ago. Glutamate, the major excitatory neurotransmitter in the central nervous system, and glutamatergic dysfunction has been implicated in mood disorders. These data provide a rationale for the pursuit of glutamatergic agents as novel therapeutic agents. Here, we review preclinical and clinical investigations of glutamatergic agents in mood disorders with a focus on depression. We begin with discussion of evidence for the rapid antidepressant effects of ketamine, followed by studies of the antidepressant efficacy of the currently marketed drugs riluzole and lamotrigine. Promising novel agents currently in development, including N-methyl-D-aspartate (NMDA) receptor modulators, 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) receptor modulators, and drugs with activity at the metabotropic glutamate (mGlu) receptors are then reviewed. Taken together, both preclinical and clinical evidence exists to support the pursuit of small molecule modulators of the glutamate system as novel therapeutic agents in mood disorders. It is hoped that by targeting neural systems outside of the monoamine system, more effective and perhaps faster acting therapeutics can be developed for patients suffering from these disabling disorders.Keywords: glutamate, mood disorders, major depressive disorder, ketamine, NMDA, AMPA
format	article
author	Murrough JW Lapidus KAB Soleimani L
author_facet	Murrough JW Lapidus KAB Soleimani L
author_sort	Murrough JW
title	Novel glutamatergic drugs for the treatment of mood disorders
title_short	Novel glutamatergic drugs for the treatment of mood disorders
title_full	Novel glutamatergic drugs for the treatment of mood disorders
title_fullStr	Novel glutamatergic drugs for the treatment of mood disorders
title_full_unstemmed	Novel glutamatergic drugs for the treatment of mood disorders
title_sort	novel glutamatergic drugs for the treatment of mood disorders
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/c642c0191b914f869c9fb57dce8d4303
work_keys_str_mv	AT murroughjw novelglutamatergicdrugsforthetreatmentofmooddisorders AT lapiduskab novelglutamatergicdrugsforthetreatmentofmooddisorders AT soleimanil novelglutamatergicdrugsforthetreatmentofmooddisorders
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Novel glutamatergic drugs for the treatment of mood disorders

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