Esketamine/Ketamine: Dual‐Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology

Esketamine and ketamine are perioperative analgesics and anesthetics widely used in Europe and the United States, but their application in China is still in early stages. They primarily act through non-competitive antagonism of the N-methyl-D-aspartate receptor (NMDAR), though they also affect multiple other receptors and pathways. Due to potential side effects and addictive properties, they are subject to regulatory controls. This review synthesizes recent research on their classical applications—analgesia, sedation, and anesthesia—as well as emerging antidepressant, anti-tumor, and anti-inflammatory effects. By integrating preclinical and clinical findings and considering limitations, the review aims to inform clinical use and future research directions for these versatile agents.

Study at a glance

Abstract

Esketamine and ketamine are perioperative analgesics and anesthetics that have been widely adopted in clinical practice in Europe and the United States. However, their application in China remains in the early stages of exploration and implementation. Esketamine and ketamine exert their effects through multiple receptors and pathways, but primarily act through non-competitive antagonism of the N-methyl-D-aspartate receptor (NMDAR). However, due to their potential side effects and addictive properties, they are subject to certain regulatory controls and are not readily included in routine pharmaceutical use. This review meticulously and systematically synthesizes the latest research progress on Esketamine and ketamine. Their classical applications, including analgesia, sedation, and anesthesia, as well as antidepressant, anti-tumor, and anti-inflammatory effects, are comprehensively covered. By integrating findings from both preclinical and clinical investigations and taking into full account potential limitations, this review aims to provide profound insights that can effectively inform the clinical utilization and future research directions of ketamine and esketamine as versatile therapeutic agents.