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Ketamine pp 47-67 | Cite as

Site of Ketamine Action on the NMDA Receptor

  • Hisashi MoriEmail author
Chapter
  • 49 Downloads

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.

Keywords

Ketamine Depression Antidepressant N-methyl-d-aspartate receptors GluN1 GluN2 GluN3 Glutamate d-serine Glycine Gene knockout mice 

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

Notes

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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© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of Molecular NeuroscienceGraduate School of Medicine and Pharmaceutical Sciences, University of ToyamaToyamaJapan

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