Neuroprotective Effects of Esketamine in Central Nervous System Disorders: Mechanisms and Cellular Targets

Esketamine (ESK), the dextrorotatory enantiomer of ketamine, is an antagonist of the N-methyl-D-aspartic acid (NMDA) receptor. ESK is considered an effective anesthetic because of its ability to mitigate postoperative pain and opioid use. Recently, it has attracted significant research attention for its fast-acting antidepressant effects. Given the advantages of ESK in both perioperative and postoperative contexts, foundational research into this molecule is progressively moving forward. Accumulating evidence suggests that ESK possesses anti-inflammatory, antiapoptotic and antioxidant characteristics in various diseases. This review summarizes the neuroprotective effects of ESK in central nervous system (CNS) disorders. ESK-mediated cellular processes, including neuronal apoptosis, microglial polarization and astrocytic functions, are also summarized. In addition, the underlying molecular mechanisms of ESK are discussed, with a focus on inflammatory pathways and signalling cascades in neurological disorders.