Ketamine and other potential glutamate antidepressants

Abstract The need for rapid acting antidepressants is widely recognised. There has been much interest in glutamate mechanisms in major depressive disorder (MDD) as a promising target for the development of new antidepressants. A single intravenous infusion of ketamine, a N-methyl- d -aspartate (NMDA...

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Bibliographic Details
Published in:Psychiatry research 2015-01, Vol.225 (1), p.1-13
Main Authors: Dutta, Arpan, McKie, Shane, Deakin, J.F. William
Format: Article
Language:English
Subjects:
Animals
Antidepressive Agents - therapeutic use
Depressive Disorder, Major - drug therapy
Glutamate
Glutamic Acid - metabolism
Humans
Ketamine
Ketamine - pharmacology
Ketamine - therapeutic use
Major depressive disorder
Memantine - therapeutic use
N-methyl-d-aspartate
Psychiatry
Receptors, AMPA - drug effects
Receptors, Metabotropic Glutamate - drug effects
Receptors, N-Methyl-D-Aspartate - drug effects
Treatment Outcome
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
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Summary:Abstract The need for rapid acting antidepressants is widely recognised. There has been much interest in glutamate mechanisms in major depressive disorder (MDD) as a promising target for the development of new antidepressants. A single intravenous infusion of ketamine, a N-methyl- d -aspartate (NMDA) receptor antagonist anaesthetic agent, can alleviate depressive symptoms in patients within hours of administration. The mechanism of action appears to be in part through glutamate release onto non-NMDA receptors including α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and metabotropic receptors. However these are also reported effects on 5-HT, dopamine and intracellular effects on the mammalian target of rapamycin (mTOR) pathway. The effects of SSRI (Selective Serotonin Reuptake Inhibitor) antidepressants may also involve alterations in NMDA function. The article reviews the effect of current antidepressants on NMDA and examines the efficacy and mechanism of ketamine. Response to ketamine is also discussed and comparison with other glutamate drugs including lamotrigine, amantadine, riluzole, memantine, traxoprodil, GLYX-13, MK-0657, RO4917523, AZD2066 and Coluracetam. Future studies need to link the rapid antidepressant effects seen with ketamine to inflammatory theories in MDD.
ISSN:0165-1781
1872-7123
DOI:10.1016/j.psychres.2014.10.028