Therapeutic Modulation of Glutamate Receptors in Major Depressive Disorder
| Autor: | Carlos A. Zarate, Nicolas D. Iadarola, Elizabeth D. Ballard, Minkyung Park, Mark J. Niciu, Allison C. Nugent, Rodrigo Machado-Vieira, Níall Lally, Brittany A. Jaso, Erica M. Richards |
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| Rok vydání: | 2017 |
| Předmět: |
Traxoprodil
glutamate AMPA receptor Pharmacology metabotropic Article 03 medical and health sciences negative allosteric modulator 0302 clinical medicine α-amino-3-hydroxyl-5-methyl-4-isoxazoleproprionic acid (AMPA) medicine Animals Humans Pharmacology (medical) Excitatory Amino Acid Agents Depressive Disorder Major major depressive disorder (MDD) Memantine antagonist General Medicine N-methyl-D-aspartate (NMDA) Antidepressive Agents 030227 psychiatry Psychiatry and Mental health Metabotropic receptor Receptors Glutamate Neurology Metabotropic glutamate receptor positive allosteric modulator Antidepressant NMDA receptor Neurology (clinical) Metabotropic glutamate receptor 2 Psychology 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Current Neuropharmacology |
| ISSN: | 1570-159X |
| DOI: | 10.2174/1570159x14666160321123221 |
| Popis: | Current pharmacotherapies for major depressive disorder (MDD) have a distinct lag of onset that can prolong distress and impairment for patients, and realworld effectiveness trials further suggest that antidepressant efficacy is limited in many patients. All currently approved antidepressant medications for MDD act primarily through monoaminergic mechanisms, e.g., receptor/reuptake agonists or antagonists with varying affinities for serotonin, norepinephrine, or dopamine. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamate and its cognate receptors are implicated in the pathophysiology of MDD, as well as in the development of novel therapeutics for this disorder. Since the rapid and robust antidepressant effects of the N-methyl-D-aspartate (NMDA) antagonist ketamine were first observed in 2000, other NMDA receptor antagonists have been studied in MDD. These have been associated with relatively modest antidepressant effects compared to ketamine, but some have shown more favorable characteristics with increased potential in clinical practice (for instance, oral administration, decreased dissociative and/or psychotomimetic effects, and reduced abuse/diversion liability). This article reviews the clinical evidence supporting the use of glutamate receptor modulators with direct affinity for cognate receptors: 1) non-competitive NMDA receptor antagonists (ketamine, memantine, dextromethorphan, AZD6765); 2) subunit (NR2B)-specific NMDA receptor antagonists (CP- 101,606/traxoprodil, MK-0657); 3) NMDA receptor glycine-site partial agonists (D-cycloserine, GLYX- 13); and 4) metabotropic glutamate receptor (mGluR) modulators (AZD2066, RO4917523/basimglurant). Several other theoretical glutamate receptor targets with preclinical antidepressant-like efficacy, but that have yet to be studied clinically, are also briefly discussed; these include α-amino-3-hydroxyl-5-methyl-4- isoxazoleproprionic acid (AMPA) agonists, mGluR2/3 negative allosteric modulators, and mGluR7 agonists. |
| Databáze: | OpenAIRE |
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