Arketamine, a new rapid-acting antidepressant: A historical review and future directions
Ji-Chun Zhang, Wei Yao, Kenji Hashimoto
Neuropharmacology August 14, 2022 DOI: 10.1016/j.neuropharm.2022.109219 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Open-label Peer reviewed |
|---|---|
| Topics | Ketamine |
| Keywords | Antidepressant Psychotherapist Pharmacology |
| Citations | 88 |
| Key findings | Arketamine may have greater potency, longer-lasting antidepressant-like effects, and fewer side effects than esketamine in preclinical and early clinical studies. |
Abstract
The N-methyl-d-aspartate receptor (NMDAR) antagonist (R,S)-ketamine causes rapid onset and sustained antidepressant actions in treatment-resistant patients with major depressive disorder (MDD) and other psychiatric disorders, such as bipolar disorder and post-traumatic stress disorder. (R,S)-ketamine is a racemic mixture consisting of (R)-ketamine (or arketamine) and (S)-ketamine (or esketamine), with (S)-enantiomer having greater affinity for the NMDAR. In 2019, an esketamine nasal spray by Johnson & Johnson was approved in the USA and Europe for treatment-resistant depression. In contrast, an increasing number of preclinical studies show that arketamine has greater potency and longer-lasting antidepressant-like effects than esketamine in rodents, despite the lower binding affinity of arketamine for the NMDAR. Importantly, the side effects, i.e., psychotomimetic and dissociative effects and abuse liability, of arketamine are less than those of (R,S)-ketamine and esketamine in animals and humans. An open-label study demonstrated the rapid and sustained antidepressant effects of arketamine in treatment-resistant patients with MDD. A phase 2 clinical trial of arketamine in treatment-resistant patients with MDD is underway. This study was designed to review the brief history of the novel antidepressant arketamine, the molecular mechanisms underlying its antidepressant actions, and future directions.
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 58
- Maintenance ketamine treatment for depression: a systematic review of efficacy, safety, and tolerability. The Lancet Psychiatry November 1, 2022
- Ketamine and its metabolites: Potential as novel treatments for depression. Neuropharmacology October 1, 2022
- Inflammation, stress and depression: an exploration of ketamine’s therapeutic profile Drug Discovery Today February 1, 2023
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment Neuropharmacology January 13, 2023
- Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics? European Archives of Psychiatry and Clinical Neuroscience February 27, 2024
and 53 more in the library
Cites 55
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
and 50 more in the library