Therapeutic Modulation of Glutamate Receptors in Major Depressive Disorder
Current Neuropharmacology March 25, 2016 Brittany A. Jaso, Mark J. Niciu, Nicolas D. Iadarola et al. 97 citations
Current antidepressants for major depressive disorder work through monoaminergic mechanisms and have a delayed onset and limited efficacy. Glutamate, the main excitatory neurotransmitter, is involved in depression's pathophysiology. Since ketamine, an NMDA receptor antagonist, showed rapid antidepressant effects in 2000, other NMDA receptor antagonists have been studied but with more modest effects. Some have advantages like oral administration and fewer side effects. This article reviews clinical evidence for glutamate receptor modulators: non-competitive NMDA antagonists (ketamine, memantine, dextromethorphan, AZD6765), NR2B-subunit antagonists (traxoprodil, MK-0657), glycine-site partial agonists (D-cycloserine, GLYX-13), and metabotropic glutamate receptor modulators (AZD2066, basimglurant). Preclinical targets like AMPA agonists and mGluR2/3 negative allosteric modulators are also discussed.