Journal article
Novel Glutamatergic Treatments for Severe Mood Disorders
Current behavioral neuroscience reports, Vol.2(4), pp.198-208
12/2015
DOI: 10.1007/s40473-015-0050-5
PMCID: PMC4725605
PMID: 26824031
Abstract
All currently approved antidepressant medications for major depressive disorder (MDD) and bipolar disorder act primarily on the monoaminergic system and have varying affinities for serotonergic, norepinephrine-ergic, and/or dopaminergic receptors. Unfortunately, these drugs are only effective in approximately two thirds of patients. Glutamate is the major excitatory neurotransmitter in the central nervous system, and the glutamatergic system has been implicated in the pathophysiology of MDD. Here, we review the putative involvement of the glutamate receptor subtypes—N-methyl-d-aspartate (NMDA), α-amino-3-hydroxyl-5-methyl-4-isoxazoleproprionic acid (AMPA), kainate, and the group I, II, and III metabotropic glutamate receptors (mGluRs)—in the development of novel and more effective treatments for mood disorders as well as preclinical and clinical trials of drugs targeting these receptors. The rapid and robust antidepressant effects of ketamine—an NMDA receptor antagonist—have been consistently replicated in multiple trials. Other glutamatergic drugs have been investigated with varying success. Here, we highlight some of the most interesting results, including the following: (1) repeated oral, intramuscular, and sublingual ketamine appears to be less robustly effective than intravenous ketamine, but also causes fewer significant adverse effects; (2) the glycine partial agonist GLYX-13 appears to be effective both as monotherapy and adjunctive treatment in the treatment of MDD. An oral analogue, NRX-1074, is currently under investigation; and (3) mGluR modulators targeting mGluR5 have demonstrated convincing preclinical results.
Details
- Title: Subtitle
- Novel Glutamatergic Treatments for Severe Mood Disorders
- Creators
- Minkyung Park - National Institute of Mental HealthMark Niciu - National Institute of Mental HealthCarlos Zarate Jr - National Institute of Mental Health
- Resource Type
- Journal article
- Publication Details
- Current behavioral neuroscience reports, Vol.2(4), pp.198-208
- DOI
- 10.1007/s40473-015-0050-5
- PMID
- 26824031
- PMCID
- PMC4725605
- NLM abbreviation
- Curr Behav Neurosci Rep
- ISSN
- 2196-2979
- eISSN
- 2196-2979
- Publisher
- Springer International Publishing; Cham
- Language
- English
- Date published
- 12/2015
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984003438602771
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