Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Nov 2;36(44):11158-11164.
doi: 10.1523/JNEUROSCI.1547-16.2016.

Ketamine: NMDA Receptors and Beyond

Charles F Zorumski  1 , Yukitoshi Izumi  2 , Steven Mennerick  2
Affiliations

Ketamine: NMDA Receptors and Beyond

Charles F Zorumski et al. J Neurosci. .

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.

Keywords: antidepressant; hippocampus; ketamine; memantine; psychotomimetic.

PubMed Disclaimer

References

    1. Abdallah CG, Sanacora G, Duman RS, Krystal JH. Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. Annu Rev Med. 2015;66:509–523. doi: 10.1146/annurev-med-053013-062946. - DOI - PMC - PubMed
    1. Anis NA, Berry SC, Burton NR, Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurons by N-methyl-aspartate. Br J Pharmacol. 1983;79:565–575. doi: 10.1111/j.1476-5381.1983.tb11031.x. - DOI - PMC - PubMed
    1. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, Kavalali ET, Monteggia LM. NMDA receptor blockade at rest triggers rapid behavioral antidepressant responses. Nature. 2011;475:91–95. doi: 10.1038/nature10130. - DOI - PMC - PubMed
    1. Baker SC, Shabir S, Georgopoulos NT, Southgate J. Ketamine-induced apoptosis in normal human urothelial cells: a direct, N-methyl-d-aspartate receptor-independent pathway characterized by mitochondrial stress. Am J Pathol. 2016;186:1267–1277. doi: 10.1016/j.ajpath.2015.12.014. - DOI - PMC - PubMed
    1. Behrens MM, Ali SS, Dao DN, Lucero J, Shekhtman G, Quick KL, Dugan LL. Ketamine-induced loss of phenotype of fast spiking interneurons is mediated by NADPH-oxidase. Science. 2007;318:1645–1647. doi: 10.1126/science.1148045. - DOI - PubMed

Publication types

LinkOut - more resources