Rapastinel, a novel glutamatergic agent with ketamine-like antidepressant actions: Convergent mechanisms.
Taro Kato, Ronald S. Duman
Pharmacology, Biochemistry, and Behavior November 13, 2019 DOI: 10.1016/j.pbb.2019.172827 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Key findings | Rapastinel produces rapid antidepressant actions without ketamine-like side effects, though recent clinical trials have been negative. |
Abstract
Conventional antidepressant medications, which act on monoaminergic systems, have significant limitations, including a time lag of weeks to months and low rates of therapeutic efficacy. Recently, clinical findings demonstrate that ketamine, a dissociative anesthetic that blocks N-methyl-d-aspartate (NMDA) receptor channel activity, causes rapid (within hours) and long-lasting (7 to 10 days) antidepressant effects. Rapastinel is a novel glutamatergic compound that acts as an NMDAR partial agonist properties, and produces rapid antidepressant actions in depressed patients and in preclinical rodent models. In addition, rapastinel has no ketamine-like side effect such as cognitive impairment and psychotomimetic symptoms. Despite recent negative clinical trials, it remains possible that rapastinel could prove effective as an alternative rapid agent with reduced side effects. In this review, we discuss the pharmacological profile of rapastinel and the molecular and cellular mechanisms underlying the rapid and sustained antidepressant actions of this novel agent.
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 19
- Neurotrophic mechanisms underlying the rapid and sustained antidepressant actions of ketamine. Pharmacology, Biochemistry, and Behavior December 9, 2019
- Novel drug developmental strategies for treatment‐resistant depression British Journal of Pharmacology November 25, 2021
- Ketamine and the Future of Rapid-Acting Antidepressants Annual Review of Clinical Psychology February 9, 2021
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment Neuropharmacology January 13, 2023
- Glutamatergic receptor and neuroplasticity in depression: Implications for ketamine and rapastinel as the rapid-acting antidepressants. Biochemical and Biophysical Research Communications 2022
and 14 more in the library
Cites 13
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014
and 8 more in the library