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Site of Ketamine Action on the NMDA Receptor

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Ketamine

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Abstract

Ketamine, an antagonist of N-methyl-d-aspartate receptors (NMDARs), produces rapid and sustained reduction of symptoms in patients with treatment-resistant depression. NMDARs are critical for neural network formation, neuronal plasticity, higher brain functions, and pathophysiology of neurodegenerative and psychiatric disorders. Recent studies have identified functional domains of diverse NMDAR subunits, as well as the site of ketamine action on NMDARs. The site of ketamine action overlaps with the site of physiological voltage-dependent Mg2+ block. Furthermore, different NMDAR GluN2 subunits contribute differentially to the sensitivity of ketamine. High-resolution analyses of the structure of the action site of ketamine on NMDARs and the mechanisms of ketamine action in vivo will contribute to the development of novel and effective antidepressant drugs.

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Abbreviations

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid

APV:

d-2-Amino-5-phosphono-valerate

ATD:

Amino-terminal domain

CNS:

Central nervous system

CTD:

Carboxy-terminal domain

GluR:

Glutamate receptor

KO:

Gene knockout

LBD:

Ligand-binding domain

LTP:

Long-term potentiation

NMDA:

N-methyl-d-aspartate

PCP:

Phencyclidine

PFC:

Prefrontal cortex

TMD:

Transmembrane domain

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Acknowledgments

I thank Dr. Hironori Izumi for the preparation of the figures. Parts of this work were supported by a Grant from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (KAKENHI, Grant No. 18K06888).

Conflict of interest: The author declares no conflicts of interest with the content of this chapter.

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  1. Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Hisashi Mori

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  1. Hisashi Mori
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Correspondence to Hisashi Mori .

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  1. Division of Clinical Neuroscience, Chiba University, Chiba, Japan

    Kenji Hashimoto

  2. Tokyo Metropolitan Institute of Medical, Tokyo, Japan

    Soichiro Ide

  3. Tokyo Metropolitan Institute of Medical, Tokyo, Japan

    Kazutaka Ikeda

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Mori, H. (2020). Site of Ketamine Action on the NMDA Receptor. In: Hashimoto, K., Ide, S., Ikeda, K. (eds) Ketamine. Springer, Singapore. https://doi.org/10.1007/978-981-15-2902-3_4

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