Ketamine for post-traumatic stress disorders and it's possible therapeutic mechanism

Muhammad Asim; Bing Wang; Bo Hao; Xiaoguang Wang

doi:10.1016/j.neuint.2021.105044

Ketamine for post-traumatic stress disorders and it's possible therapeutic mechanism

Neurochem Int. 2021 Jun:146:105044. doi: 10.1016/j.neuint.2021.105044. Epub 2021 Apr 13.

Authors

Muhammad Asim¹, Bing Wang², Bo Hao³, Xiaoguang Wang⁴

Affiliations

¹ Key Laboratory of Neuroscience, Department of Biomedical Science, City University of Hong Kong, Kowloon Tong, Hong Kong; Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
² Department of Neurosurgery, The Second Affiliated Hospital, University of South China, Hengyang, China.
³ Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
⁴ Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China. Electronic address: wxguang@mail.sysu.edu.cn.

PMID: 33862176
DOI: 10.1016/j.neuint.2021.105044

Abstract

Posttraumatic stress disorder (PTSD) is a devastating medical illness, for which currently available pharmacotherapies have poor efficacy. Accumulating evidence from clinical and preclinical animal investigations supports that ketamine exhibits a rapid and persistent effect against PTSD, though the underlying molecular mechanism remains to be clarified. In this literature review, we recapitulate the achievements from early ketamine studies to the most up-to-date discoveries, with an effort to discuss an inclusive therapeutic role of ketamine for PTSD treatment and its possible therapeutic mechanism. Ketamine seems to have an inimitable mechanism of action entailing glutamate modulation via actions at the N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, as well as downstream activation of brain-derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR) signaling pathways to potentiate synaptic plasticity.

Keywords: CCK; Ketamine; NMDAR; PTSD.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Excitatory Amino Acid Antagonists / pharmacology
Excitatory Amino Acid Antagonists / therapeutic use*
Humans
Ketamine / pharmacology
Ketamine / therapeutic use*
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Receptors, N-Methyl-D-Aspartate / metabolism
Stress Disorders, Post-Traumatic / drug therapy*
Stress Disorders, Post-Traumatic / metabolism

Substances

Excitatory Amino Acid Antagonists
Receptors, N-Methyl-D-Aspartate
Ketamine