Ketamine's Dose Related Multiple Mechanisms of Actions: Dissociative Anesthetic to Rapid Antidepressant.
E. Lavender, Mika Hirasawa-Fujita, E. Domino
Behavioural Brain Research May 8, 2020 DOI: 10.1016/j.bbr.2020.112631 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Key findings | The authors argue that ketamine's antidepressant effects likely involve mechanisms beyond NMDA receptor antagonism, including AMPA receptors, the mTOR pathway, monoaminergic, sigma-1, cholinergic, opioid, and cannabinoid systems, and certain ion channels. They also review the distinct pharmacology of ketamine's enantiomers and metabolites and suggest that insight into these multiple mechanisms could support further clinical development. |
Abstract
Ketamine induces safe and effective anesthesia and displays unusual cataleptic properties that gave rise to the term dissociative anesthesia. Since 1970, clinicians only utilized the drug as an anesthetic or analgesic for decades, but ketamine was found to have rapid acting antidepressant effects in 1990s. Accumulated evidence exhibits NMDAR antagonism may not be the only mechanism of ketamine. The contributions of AMPA receptor, mTor signal pathway, monoaminergic system, sigma-1 receptor, cholinergic, opioid and cannabinoid systems, as well as voltage-gated calcium channels and hyperpolarization cyclic nucleotide gated channels are discussed for the antidepressant effects. Also the effects of ketamine's enantiomers and metabolites are reviewed. Furthermore ketamine's anesthetic and analgesic mechanisms are briefly revisited. Overall, pharmacology of ketamine, its enantiomers and metabolites is very unique. Insight into multiple mechanisms of action will provide further development and desirable clinical effects of ketamine.
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 23
- Ketamine: Mechanisms and Relevance to Treatment of Depression. Annual Review of Medicine September 20, 2023
- Ketamine: Neuroprotective or Neurotoxic? Frontiers in Neuroscience September 10, 2021
- Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder Neuropharmacology January 6, 2023
- Use and abuse of dissociative and psychedelic drugs in adolescence Pharmacology, Biochemistry, and Behavior January 27, 2021
- Effects of intranasal (S)-ketamine on Veterans with co-morbid treatment-resistant depression and PTSD: A retrospective case series EClinicalMedicine May 7, 2022
and 18 more in the library
Cites 36
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine Anesthesia & Analgesia November 1, 1998
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
and 31 more in the library