Neuroprotective Effects of Esketamine in Central Nervous System Disorders: Mechanisms and Cellular Targets
Basic & Clinical Pharmacology & Toxicology – March 11, 2026
Source: OpenAlex
Summary
Esketamine (ESK), an NMDA receptor antagonist, shows promise beyond anesthesia, boasting antidepressant effects that can rapidly alleviate symptoms in major depression. In various studies involving over 1,000 participants, ESK demonstrated significant neuroprotective properties, including anti-inflammatory and antioxidant effects. It also influences critical cellular processes such as neuronal apoptosis and microglial polarization. These findings highlight ESK's potential in treating central nervous system disorders while addressing postoperative pain and reducing opioid use, marking a significant advancement in pharmacology and neuroscience.
Abstract
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.