Novel Glutamatergic Treatments for Severe Mood Disorders

Current Behavioral Neuroscience Reports
Minkyung ParkCarlos A Zarate

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 MDD 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: 1) repeated oral, intramuscular, and sublingual ketamine appears to be less robu...Continue Reading

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Citations

Jan 17, 2017·Expert Review of Neurotherapeutics·Ricardo P GarayPierre-Michel Llorca
Feb 22, 2018·Harvard Review of Psychiatry·Ioline D HenterCarlos A Zarate
Nov 18, 2018·The International Journal of Neuropsychopharmacology·Bashkim KadriuCarlos A Zarate
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Dec 22, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Gara Arteaga-HenriquezHemmo A Drexhage
Jul 31, 2021·World Journal of Psychiatry·Adejoke Yetunde Onaolapo, Olakunle James Onaolapo

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