Ketamine pp 105-125 | Cite as

Antidepressant Actions of Ketamine and Its Two Enantiomers

  • Lijia Chang
  • Yan Wei
  • Kenji HashimotoEmail author


The N-methyl-d-aspartate receptor antagonist ketamine has been widely used as an off-label medication to treat depression because it elicits rapid and robust antidepressant effects in treatment-resistant patients with depression. (R,S)-ketamine is a racemic mixture containing equal amounts of (R)-ketamine (or arketamine) and (S)-ketamine (or esketamine). On March 5, 2019, the United States Food and Drug Administration approved an (S)-ketamine nasal spray for treatment-resistant depression. In contrast, (R)-ketamine has been reported to have a greater potency and longer-lasting antidepressant effects than (S)-ketamine in rodent models of depression. However, the precise mechanisms underlying the robust antidepressant effects of ketamine enantiomers remain unknown. In this chapter, we discuss recent findings on the antidepressant actions of two enantiomers of ketamine.


Arketamine Ketamine Esketamine 



This study was supported by grant from AMED, Japan (to K.H., JP19dm0107119). Dr. Lijia Chang was supported by the Japan China Sasakawa Medical Fellowship (Tokyo, Japan). Dr. Yan Wei (Southwest Medical University, China) was supported by the China Scholarship Council (China).

Disclosure Statement: Dr. Hashimoto is the inventor of filed patent applications on “The use of R-ketamine in the treatment of psychiatric diseases” by the Chiba University. Dr. Hashimoto also declares that he has received research support and consultant from Dainippon Sumitomo, Otsuka, and Taisho.


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© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Division of Clinical NeuroscienceChiba University Center for Forensic Mental HealthChibaJapan
  2. 2.Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cadiovascular Disease, Institute of Cardiovascular ResearchSouthwest Medical UniversityLuzhouChina

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