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Ketamine: NMDA Receptors and Beyond

Charles F Zorumski, Yukitoshi Izumi, Steven Mennerick

Journal of Neuroscience November 2, 2016 DOI: 10.1523/jneurosci.1547-16.2016 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Viewpoint Peer reviewed
Topics Esketamine Ketamine
Citations 252
Key points Ketamine's antidepressant effects may not depend on NMDAR blockade, though NMDARs are important for some psychiatric effects.

Abstract

Human studies examining the effects of the dissociative anesthetic ketamine as a model for psychosis and as a rapidly acting antidepressant have spurred great interest in understanding ketamine's actions at molecular, cellular, and network levels. Although ketamine has unequivocal uncompetitive inhibitory effects on N-methyl-d-aspartate receptors (NMDARs) and may preferentially alter the function of NMDARs on interneurons, recent work has questioned whether block of NMDARs is critical for its mood enhancing actions. In this viewpoint, we examine the evolving literature on ketamine supporting NMDARs as important triggers for certain psychiatric effects and the possibility that the antidepressant trigger is unrelated to NMDARs. The rapidly evolving story of ketamine offers great hope for untangling and treating the biology of both depressive and psychotic illnesses.