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

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.