Neuroprotective Effects of Esketamine in Central Nervous System Disorders: Mechanisms and Cellular Targets
Chendi Zhao, Yang Wang, Jinglang Wu, Hong Cheng
Basic & Clinical Pharmacology & Toxicology March 11, 2026 DOI: 10.1111/bcpt.70221 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine Esketamine |
| Keywords | Neuroprotection Central nervous system Pharmacology Anesthetic Antagonist Antidepressant Glutamate receptor Premovement neuronal activity Opioid Anesthesia Signalling pathways Nmda receptor |
| Key findings | Esketamine possesses neuroprotective effects in central nervous system disorders through anti-inflammatory, antiapoptotic, and antioxidant mechanisms. |
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.