Purpose Of Review: To explore the convergent downstream pathways of ketamine and rapastinel and drive further development of identification for following generational rapid-acting antidepressants in the synaptic process.
Recent Findings: Ketamine is an NMDAR antagonist and is proven effective in depression for the rapid and sustained antidepressant response, while rapastinel is an NMDAR positive allosteric modulator, producing antidepressant effects like ketamine with no severe side effects. The common antidepressant effects of ketamine and rapastinel are BDNF and mTORC1 pathway in synaptic plasticity.
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Effects of psychoplastogens on blood levels of brain-derived neurotrophic factor (BDNF) in humans: a systematic review and meta-analysis.
Mol Psychiatry
February 2025
Molecular Psychiatry Lab, Department of Medicine, University of Fribourg, Fribourg, Switzerland.
Article Synopsis
- A meta-analysis was conducted to evaluate whether psychoplastogens like ketamine and psychedelics increase peripheral BDNF levels in humans, which have been suggested as biomarkers for neuroplasticity.
- The analysis included data from 29 studies and found no significant evidence that these substances elevate peripheral BDNF levels, regardless of various factors such as drug type, dosage, or participant characteristics.
- The findings imply that peripheral BDNF may not be a reliable marker for assessing neuroplasticity changes in humans after psychoplastogen administration, highlighting potential discrepancies between preclinical and human studies.
Psychoplastogens: A Novel Therapeutic Approach for Neurological Diseases and Disorders.
ACS Med Chem Lett
September 2023
Usona Institute, Fitchburg, Wisconsin 53711-5300, United States.
Neurological diseases often involve changes in synaptic connectivity and plasticity. Psychoplastogens, substances that stimulate neuronal growth and enhance neural structures, show promise in mitigating these changes. They activate key biological targets, including AMPA receptors, TrkB, and mTOR.
View Article and Find Full Text PDFRepeated administration of rapastinel produces exceptionally prolonged rescue of memory deficits in phencyclidine-treated mice.
Behav Brain Res
August 2022
Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, IL, USA. Electronic address:
Rapastinel, a positive N-methyl-D-aspartate receptor (NMDAR) modulator with rapid-acting antidepressant properties, rescues memory deficits in rodents. We have previously reported that a single intravenous dose of rapastinel, significantly, but only transiently, prevented and rescued deficits in the novel object recognition (NOR) test, a measure of episodic memory, produced by acute or subchronic administration of the NMDAR antagonists, phencyclidine (PCP) and ketamine. Here, we tested the ability of single and multiple subcutaneous doses per day of rapastinel to restore NOR and operant reversal learning (ORL) deficits in subchronic PCP-treated mice.
View Article and Find Full Text PDFGlutamatergic receptor and neuroplasticity in depression: Implications for ketamine and rapastinel as the rapid-acting antidepressants.
Biochem Biophys Res Commun
February 2022
Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, China. Electronic address:
Purpose Of Review: To explore the convergent downstream pathways of ketamine and rapastinel and drive further development of identification for following generational rapid-acting antidepressants in the synaptic process.
Recent Findings: Ketamine is an NMDAR antagonist and is proven effective in depression for the rapid and sustained antidepressant response, while rapastinel is an NMDAR positive allosteric modulator, producing antidepressant effects like ketamine with no severe side effects. The common antidepressant effects of ketamine and rapastinel are BDNF and mTORC1 pathway in synaptic plasticity.
Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder.
Cochrane Database Syst Rev
September 2021
Oxford Health NHS Foundation Trust, Oxford, UK.
Background: Many studies have recently been conducted to assess the antidepressant efficacy of glutamate modification in mood disorders. This is an update of a review first published in 2015 focusing on the use of glutamate receptor modulators in unipolar depression.
Objectives: To assess the effects - and review the acceptability and tolerability - of ketamine and other glutamate receptor modulators in alleviating the acute symptoms of depression in people with unipolar major depressive disorder.
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