The role of NMDARs in the anesthetic and antidepressant effects of ketamine.
Liang Zhou, Jingjing Duan
CNS Neuroscience & Therapeutics April 1, 2024 DOI: 10.1111/cns.14464 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine Esketamine |
| Keywords | Nmdars Anesthetic effects Antidepressant effects Metabolites |
| Key findings | Both anesthetic and antidepressant effects of ketamine are thought to be mediated by NMDAR inhibition, but the roles of NMDARs in antidepressant effects are complicated and controversial. |
Abstract
As a phencyclidine (PCP) analog, ketamine can generate rapid-onset and substantial anesthetic effects. Contrary to traditional anesthetics, ketamine is a dissociative anesthetic and can induce loss of consciousness in patients. Recently, the subanaesthetic dose of ketamine was found to produce rapid-onset and lasting antidepressant effects. However, how different concentrations of ketamine can induce diverse actions remains unclear. Furthermore, the molecular mechanisms underlying the NMDAR-mediated anesthetic and antidepressant effects of ketamine are not fully understood. In this review, we have introduced ketamine and its metabolism, summarized recent advances in the molecular mechanisms underlying NMDAR inhibition in the anesthetic and antidepressant effects of ketamine, explored the possible functions of NMDAR subunits in the effects of ketamine, and discussed the future directions of ketamine-based anesthetic and antidepressant drugs. Both the anesthetic and antidepressant effects of ketamine were thought to be mediated by N-methyl-D-aspartate receptor (NMDAR) inhibition. The roles of NMDARs have been extensively studied in the anaesthetic effects of ketamine. However, the roles of NMDARs in antidepressant effects of ketamine are complicated and controversial.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 6
- Ketamine, an Old–New Drug: Uses and Abuses Pharmaceuticals December 21, 2023
- A scientometric analysis of research on the role of NMDA receptor in the treatment of depression. Frontiers in Pharmacology 2024
- S-ketamine ameliorates post-stroke depression in mice via attenuation of neuroinflammation, synaptic restoration, and BDNF pathway activation. Biochemical and Biophysical Research Communications July 8, 2025
- Ketamine: An emerging agent in the management of neuropsychiatric disorders. Asian Journal of Psychiatry April 1, 2025
- Sex specific effects of ketamine, but not other glutamate receptor modulators, on ethanol self-administration and reinstatement of ethanol seeking in rats. Psychopharmacology April 8, 2025
and 1 more in the library
Cites 62
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- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
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and 57 more in the library