ArticleBehavioural brain research2015
Rapastinel (GLYX-13) has therapeutic potential for the treatment of post-traumatic stress disorder: Characterization of a NMDA receptor-mediated metaplasticity process in the medial prefrontal cortex of rats.
Article in Behavioural brain research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents.Frontiers in pharmacology · 2022Pooled it
- New advances in small molecule drugs targeting NMDA receptors.Acta pharmacologica Sinica · 2026Review
- Depression-like effects induced by chronic unpredictable mild stress in mice are rapidly reversed by a partial negative allosteric modulator of mGluPsychopharmacology · 2025Article
- Ginkgo Biloba as a niche theme cognitive enhancer agent, 1420 dokumen of Scopus database. A bibliometric study from 1988 to 2024.F1000Research · 2025Article
- The Antidepressant-like Activity and Cognitive Enhancing Effects of the Combined Administration of (Pharmaceuticals (Basel, Switzerland) · 2023Article
- ERK/mTOR signaling may underlying the antidepressant actions of rapastinel in mice.Translational psychiatry · 2022Article
- Melamine disrupts spatial reversal learning and learning strategy via inhibiting hippocampal BDNF-mediated neural activity.PloS one · 2021Article
- Medial PFC AMPA receptor and BDNF signaling are required for the rapid and sustained antidepressant-like effects of 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Diminished Fear Extinction in Adolescents Is Associated With an Altered Somatostatin Interneuron-Mediated Inhibition in the Infralimbic Cortex.Biological psychiatry · 2019Article
- Region- and time-dependent gene regulation in the amygdala and anterior cingulate cortex of a PTSD-like mouse model.Molecular brain · 2019Article
- Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects.The international journal of neuropsychopharmacology · 2019Article
- Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects.Nature communications · 2019Article
- Convergent Mechanisms Underlying Rapid Antidepressant Action.CNS drugs · 2018Review
- NYX-2925 Is a Novel NMDA Receptor-Specific Spirocyclic-β-Lactam That Modulates Synaptic Plasticity Processes Associated with Learning and Memory.The international journal of neuropsychopharmacology · 2018Article
- IGFBP2 Produces Rapid-Acting and Long-Lasting Effects in Rat Models of Posttraumatic Stress Disorder via a Novel Mechanism Associated with Structural Plasticity.The international journal of neuropsychopharmacology · 2017Article
- GLYX-13 Produces Rapid Antidepressant Responses with Key Synaptic and Behavioral Effects Distinct from Ketamine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Assessment of a glycine uptake inhibitor in animal models of effort-related choice behavior: implications for motivational dysfunctions.Psychopharmacology · 2017Article
- The chronic mild stress (CMS) model of depression: History, evaluation and usage.Neurobiology of stress · 2017Review
- Rapid Acting Antidepressants in Chronic Stress Models: Molecular and Cellular Mechanisms.Chronic stress (Thousand Oaks, Calif.) · 2017Article
- Synaptic Plasticity, Metaplasticity and Depression.Current neuropharmacology · 2017Review
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10 authors.
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Abstract
Rapastinel (GLYX-13) is a NMDA receptor modulator with glycine-site partial agonist properties. It is a robust cognitive enhancer and shows rapid and long-lasting antidepressant properties in both animal models and in humans. Contextual fear extinction (CFE) in rodents has been well characterized and used extensively as a model to study the neurobiological mechanisms of post-traumatic stress disorder (PTSD). Since CFE is NMDA receptor modulated and neural circuitry in the medial prefrontal cortex (MPFC) regulates both depression and PTSD, studies were undertaken to examine the effects of rapastinel for its therapeutic potential in PTSD and to use rapastinel as a tool to study its underlying glutamatergic mechanisms. A 21-day chronic mild unpredictable stress (CUS) rat model was used to model depression and PTSD. The effects of CUS alone compared to No CUS controls, and the effects of rapastinel (3 mg/kg IV) on CUS-treated animals were examined. The effect of rapastinel was first assessed using CUS-treated rats in three depression models, Porsolt, sucrose preference, and novelty-induced hypophagia tests, and found to produce a complete reversal of the depressive-like state in each model. Rapastinel was then assessed in a MPFC-dependent positive emotional learning paradigm and in CFE and again a reversal of the impairments induced by CUS treatment was observed. Both synaptic plasticity and metaplasticity, as measured by the induction of long-term potentiation in rat MPFC slice preparations, was found to be markedly impaired in CUS-treated animals. This impairment was reversed when CUS-treated rats were administered rapastinel and tested 24 h later. Transcriptomic analysis of MPFC mRNA expression in CUS-treated rats corroborated the link between rapastinel's behavioral effects and synaptic plasticity. A marked enrichment in both the LTP and LTD connectomes in rapastinel-treated CUS rats was observed compared to CUS-treated controls. The effects of rapastinel on depression models, PEL, and most importantly on CFE demonstrate the therapeutic potential of rapastinel for the treatment of PTSD. Moreover, rapastinel appears to elicit its therapeutic effects through a NMDA receptor-mediated, LTP-like, metaplasticity process in the MPFC.
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