Ketamine – More mechanisms of action than just NMDA blockade
Jamie Sleigh, Martyn Harvey, Logan J. Voss, Bill Denny
Trends in Anaesthesia and Critical Care March 22, 2014 DOI: 10.1016/j.tacc.2014.03.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Glutamatergic Nmda receptor Blockade Sedation Cholinergic Antidepressant Opioid Pharmacology Anesthesia Glutamate receptor Hippocampus |
| Citations | 441 |
| Key findings | Ketamine's long-lasting effects on chronic pain and depression are probably mediated by a secondary increase in structural synaptic connectivity from a neuronal response to a hyper-glutamatergic state. |
Abstract
Ketamine has been in clinical use for over half a century, yet its precise mechanisms of action remain mysterious for the large part. Its hypnotic effects appear to be largely mediated by blockade of NMDA and HCN1 receptors, but cholinergic, aminergic, and opioid systems appear to play both a positive and negative modulatory role in both sedation and analgesia. Ketamine's effects in chronic pain, and as an antidepressant, far outlast the actual drug levels, and are probably mediated by a secondary increase in structural synaptic connectivity that is mediated by a neuronal response to the ketamine-induced hyper-glutamatergic state.
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 107
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism American Journal of Psychiatry August 29, 2018
- Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Journal of Affective Disorders September 23, 2020
- Ketamine: 50 Years of Modulating the Mind Frontiers in Human Neuroscience November 29, 2016
- Ketamine: NMDA Receptors and Beyond Journal of Neuroscience November 2, 2016
and 102 more in the library
Cites 8
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- Ketamine for chronic pain: risks and benefits British Journal of Clinical Pharmacology February 21, 2013
- A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats Anesthesiology October 1, 2011
- Depression and Pain Anesthesiology October 1, 2011
- Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology January 2012
and 3 more in the library