- |||||||||| Nectiv (traxoprodil) / Pfizer, rapastinel (GLYX-13) / AbbVie
A circuit-based, neurobehavioral assay for preclinical antidepressant profiling (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7265; More precise methods of measuring rapid changes in neuroplasticity, including neuroimaging and stimulation-based methods, are recommended for future studies attempting to translate preclinical findings to humans. Data were analyzed using a linear mixed effects model (LMM) with condition (baseline, post-treatment) and dose (vehicle, low, moderate, high) as fixed effects, focusing on 15 metrics for drug profiling and comparative analysis.We tested a panel of 12 compounds developed for Major Depressive Disorder (MDD) including Ketamine, Rapastinel, Traxoprodil, and Psilocin, all of which have
- |||||||||| rapastinel (GLYX-13) / AbbVie
Journal: Psychoplastogens: A Novel Therapeutic Approach for Neurological Diseases and Disorders. (Pubmed Central) - Sep 22, 2023 In clinical trials, psychedelic psychoplastogens have demonstrated antidepressant, anxiolytic, and anti-addictive effects. The research described in this Patent Highlight suggests the potential for novel therapies in neurological disorders that leverage psychoplastogens, which modulate synaptic connections and plasticity.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Preclinical, Journal: Models of Affective Illness: Chronic Mild Stress in the Rat. (Pubmed Central) - Mar 14, 2023 For example, the CMS-induced deficits can be reversed by acute or sub-chronic application of treatments that act rapidly in depressed patients, such as deep brain stimulation (DBS), ketamine, and scopolamine, as well as several compounds that have yet to be tested in humans but have fast-onset antidepressant-like effects in animals, such as the 5-HT-1A biased agonists NLX-101 and GLYX-13...Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Induction of chronic mild stress in rats as a model of depression and treatment-resistant depression.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Preclinical, Journal: ERK/mTOR signaling may underlying the antidepressant actions of rapastinel in mice. (Pubmed Central) - Dec 23, 2022 Based on previous and our supplementary data that showed the pivotal role of on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in the rapid release of VGF and BDNF and activation of TrkB by a single dose of rapastinel, we postulate that the antidepressant-like effects of single or repeated administration of rapastinel may result in the rapid release of VGF and BDNF or ERK/mTOR signaling pathway-mediated VGF/BDNF/TrkB autoregulatory feedback loop respectively. Our current work adds new knowledge to the molecular mechanisms that underlie the antidepressant-like actions of rapastinel in mice.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Journal: Rapastinel accelerates loss of withdrawal signs after repeated morphine and blunts relapse to conditioned place preference. (Pubmed Central) - Oct 28, 2022 Rapastinel did not affect extinction of CPP, but rapastinel-treated animals spent significantly less time in the previously morphine-paired side than saline-treated animals during the relapse trial. These findings of accelerated loss of withdrawal signs and blunted relapse to CPP suggest that rapastinel could provide an adjunctive therapy for opioid dependence during initiation of pharmacotherapy for opioid dependence.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Preclinical, Journal: Rapastinel alleviates the neurotoxic effect induced by NMDA receptor blockade in the early postnatal mouse brain. (Pubmed Central) - Feb 19, 2022 Here we found a remarkable neuroprotective effect of rapastinel against apoptosis induced by the NMDAR antagonist MK-801 in comparison to that elicited by clozapine and the mGlu2/3 agonist LY354740. These results suggest the potential therapeutic/prophylactic effect of rapastinel in ameliorating deleterious effects induced by NMDAR blockade during neurodevelopment.
- |||||||||| ketamine / Generic mfg.
Journal: Cell-type specific modulation of NMDA receptors triggers antidepressant actions. (Pubmed Central) - Feb 1, 2022 The results also demonstrate that Drd1-expressing pyramidal neurons in mPFC mediate the rapid antidepressant actions of ketamine and rapastinel. Together, these results demonstrate unique initial cellular triggers as well as converging effects on Drd1-pyramidal cell signaling that underlie the antidepressant actions of NMDAR-positive modulation vs. NMDAR blockade.
- |||||||||| Review, Journal: Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status. (Pubmed Central) - Jan 7, 2022
Furthermore, to date, most have demonstrated relatively modest effects compared with (R,S)-ketamine and esketamine, though some have shown more favorable characteristics. Of these novel agents, the most promising, and the ones for which the most evidence exists, appear to be those targeting ionotropic glutamate receptors.
- |||||||||| ketamine / Generic mfg., atomoxetine / Generic mfg., memantine / Generic mfg.
Clinical, Review, Journal: Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. (Pubmed Central) - Nov 29, 2021 The evidence for use of the remaining glutamate receptor modulators is limited as very few trials were included in the meta-analyses for each comparison and the majority of comparisons included only one study. Long term non-inferiority RCTs comparing repeated ketamine and esketamine, and rigorous real-world monitoring are needed to establish comprehensive data on safety and efficacy.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Journal: Characterization hiPSC-derived neural progenitor cells and neurons to investigate the role of NOS1AP isoforms in human neuron dendritogenesis. (Pubmed Central) - Oct 20, 2021 Treatment of human iPSC-derived neurons with D-serine, but not clozapine, haloperidol, fluphenazine, or GLYX-13, results in a reduction in endogenous NOS1AP-L, but not NOS1AP-S, protein expression; however, D-serine treatment does not reverse decreases in dendrite number mediated by overexpression of NOS1AP isoforms. In summary, we demonstrate how an in vitro model of human neuronal development can help in understanding the etiology of schizophrenia and can also be used as a platform to screen drugs for patients.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Review, Journal: Rapid acting antidepressants in the mTOR pathway: current evidence. (Pubmed Central) - Oct 1, 2021 It can be understood that modulating mTOR pathway for rapid onset of antidepressant effect in MDD is not without challenges as some of the drugs have failed in advanced stages of clinical trials. However, considering the recent approval of esketamine as a breakthrough in decades, fast acting antidepressants in the mTOR pathway may have promising prospects in the drug discovery pipeline.
- |||||||||| ganaxolone oral (CCD-1042) / Marinus
Review, Journal: Emerging Therapeutics Based on the Amino Acid Neurotransmitter System: An Update on the Pharmaceutical Pipeline for Mood Disorders. (Pubmed Central) - Jun 16, 2021 We cover both glutamate-targeting drugs such as: esketamine, AVP-786, REL-1017, AXS-05, rapastinel (GLYX-13), AV-101, NRX-101; as well as GABA-targeting drugs such as: brexanolone (SAGE-547), ganaxolone, zuranolone (SAGE-217), and PRAX-114. We focus the review on phase-II and phase-III clinical trials and evaluate the extant data and progress of these compounds.
- |||||||||| Spravato (esketamine intranasal) / J&J, bupropion/dextromethorphan (AXS-05) / Axsome Therap, rapastinel (GLYX-13) / AbbVie
[VIRTUAL] Efficacy of Non-Ketamine Glutamatergic Agents in the Treatment of Major Depressive Disorder – the Promise, the Pitfalls, and the Evidence () - Apr 13, 2021 - Abstract #ASCP2021ASCP_189; Finally, we will also discuss the potential efficacy for the most widely studied glutamatergic compound, intranasal esketamine, as a potential maintenance agent in subjects who have responded to IV acute phase racemic ketamine. Learning Objectives To evaluate the efficacy of novel, non-ketamine, glutamatergic agents for the treatment of Major Depressive Disorder To compare the efficacy IV racemic ketamine with intranasal esketamine in the acute and long-term treatment of Major Depressive Disorder
- |||||||||| Clinical, Journal: Keeping up with the clinical advances: depression. (Pubmed Central) - Aug 4, 2020
Novel therapeutics have the potential to improve both patient mood symptomatology and economical productivity, reducing the debased human capital costs associated with MDD. Furthermore, a selection of therapeutic targets provides diverse treatment options which may be beneficial to the patient considering the heterogeneity of MDD.
- |||||||||| Journal: Rapid-acting antidepressants. (Pubmed Central) - Apr 12, 2020
Less clinical data are currently available for psychedelic drugs such as psilocybin, lysergic acid diethylamide, and ayahuasca...Compounds currently in clinical development include the NMDA receptor antagonist (R)-ketamine, the NMDA receptor modulator, GLYX-13 (Rapastinel), and the AMPA receptor potentiator TAK-653...These include mGlu2/3 receptor antagonists, AMPA receptor potentiators, and negative allosteric modulators of GABA(α5) receptors. In all cases, molecules exist that could be used to provide clinical proof of concept testing.
- |||||||||| sirolimus / Generic mfg.
Clinical, Journal: Role of a VGF/BDNF/TrkB Autoregulatory Feedback Loop in Rapid-Acting Antidepressant Efficacy. (Pubmed Central) - Dec 21, 2019 Similar to ketamine, the rapid antidepressant actions of TLQP-62 require BDNF expression, mTOR activation (rapamycin-sensitive), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activation (NBQX-sensitive) and are associated with GluR1 insertion. We review recent findings that identify a rapidly induced autoregulatory feedback loop, which likely plays a critical role in sustained efficacy of rapid-acting antidepressants, depression-like behavior, and cognition, and requires VGF, its C-terminal peptide TLQP-62, BDNF/TrkB signaling, the mTOR pathway, and AMPA receptor activation and insertion.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Trial termination: Open Label Extension for GLYX13-C-202, NCT01684163 (clinicaltrials.gov) - Nov 27, 2019 P2, N=61, Terminated, We review recent findings that identify a rapidly induced autoregulatory feedback loop, which likely plays a critical role in sustained efficacy of rapid-acting antidepressants, depression-like behavior, and cognition, and requires VGF, its C-terminal peptide TLQP-62, BDNF/TrkB signaling, the mTOR pathway, and AMPA receptor activation and insertion. Completed --> Terminated; Patients from this study were rolled into RAP-MD-99.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Review, Journal: Rapastinel, a novel glutamatergic agent with ketamine-like antidepressant actions: Convergent mechanisms. (Pubmed Central) - Nov 20, 2019 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.
- |||||||||| psilocybin / Compass Pathways, rapastinel (GLYX-13) / Allergan
Journal: Rapid-Acting Antidepressants. (Pubmed Central) - Nov 8, 2019 Promising clinical findings exist for several compounds including ketamine and other NMDA receptor antagonists, scopolamine, and psilocybin. Two compounds are in late stage clinical development: GLYX-13 (Rapastinel) and eskekamine.
- |||||||||| rapastinel (GLYX-13) / Allergan
Review, Journal: The glycine site of NMDA receptors: A target for cognitive enhancement in psychiatric disorders. (Pubmed Central) - Sep 28, 2019 Six glycine site modulators with pro-cognitive and antidepressant properties were identified: d-serine (co-agonist), d-cycloserine (partial agonist), d-alanine (co-agonist), glycine (agonist), sarcosine (co-agonist) and rapastinel (partial agonist)...Taken together, preliminary results suggest that the glycine site of NMDARs is a promising target to ameliorate symptoms of depression and cognitive dysfunction. Additional rigorously designed clinical studies are required to determine the cognitive effects of these agents in MDD.
- |||||||||| rapastinel (GLYX-13) / Allergan
Journal: BDNF release and signaling are required for the antidepressant actions of GLYX-13. (Pubmed Central) - Aug 3, 2019 Finally, we examined the role of the Rho GTPase proteins by injecting a selective inhibitor into the mPFC and found that activation of Rac1 but not RhoA is involved in the antidepressant effects of GLYX-13. Together, these findings indicate that enhanced release of BDNF through exocytosis caused by activation of VDCCs and subsequent TrkB-Rac1 signaling is required for the rapid and sustained antidepressant effects of GLYX-13.Molecular Psychiatry advance online publication, 5 December 2017; doi:10.1038/mp.2017.220.
- |||||||||| ganaxolone oral (CCD-1042) / Marinus
Review, Journal: A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems. (Pubmed Central) - Aug 3, 2019 Here, we review progress in the development of compounds that act on these systems as well as their purported mechanisms of action. We include glutamate-targeting drugs, such as racemic ketamine, esketamine, lanicemine (AZD6765), traxoprodil (CP-101,606), EVT-101, rislenemdaz (CERC-301/MK-0657), AVP-786, AXS-05, rapastinel (formerly GLYX-13), apimostinel (NRX-1074/AGN-241660), AV-101, NRX-101, basimglurant (RO4917523), decoglurant (RG-1578/RO4995819), tulrampator (CX-1632/S-47445), and riluzole; and GABA-targeting agents, such as brexanolone (SAGE-547), ganaxolone, and SAGE-217.
- |||||||||| memantine / generics
Journal: NMDA Antagonists for Treatment-Resistant Depression. (Pubmed Central) - Jul 24, 2019 ...Of the other investigational agents, CERC-301 and rapastinel remain in clinical development...Research is still needed to determine the appropriate dose, schedule, and ways to mitigate against unwanted side effects of NMDA receptor blockade. These hurdles need to be overcome before ketamine and similar agents can be prescribed routinely to patients.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Monotherapy: Study of Rapastinel as Monotherapy in Patients With MDD (clinicaltrials.gov) - Jul 18, 2019 P3, N=439, Terminated, These hurdles need to be overcome before ketamine and similar agents can be prescribed routinely to patients. N=690 --> 439 | Trial completion date: Feb 2020 --> Jul 2019 | Recruiting --> Terminated | Trial primary completion date: Feb 2020 --> Jul 2019; Business decision to stop the program.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: A Study of Rapastinel for Rapid Treatment of Depression and Suicidality in Major Depressive Disorder (clinicaltrials.gov) - Jul 18, 2019 P2, N=138, Terminated, N=690 --> 439 | Trial completion date: Feb 2020 --> Jul 2019 | Recruiting --> Terminated | Trial primary completion date: Feb 2020 --> Jul 2019; Business decision to stop the program. N=300 --> 138 | Trial completion date: Jan 2020 --> Jun 2019 | Recruiting --> Terminated | Trial primary completion date: Jan 2020 --> Jun 2019; Study stopped due to business reasons.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Enrollment change, Trial withdrawal, Monotherapy: Study of Rapastinel as Monotherapy in Major Depressive Disorder (MDD) (clinicaltrials.gov) - Jul 18, 2019 P3, N=0, Withdrawn, N=300 --> 138 | Trial completion date: Jan 2020 --> Jun 2019 | Recruiting --> Terminated | Trial primary completion date: Jan 2020 --> Jun 2019; Study stopped due to business reasons. N=690 --> 0 | Not yet recruiting --> Withdrawn
- |||||||||| rapastinel (GLYX-13) / AbbVie
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Monotherapy: Study of Rapastinel as Monotherapy in Patients With Major Depressive Disorder (MDD) (clinicaltrials.gov) - Jul 18, 2019 P3, N=50, Terminated, N=690 --> 0 | Not yet recruiting --> Withdrawn N=690 --> 50 | Trial completion date: Dec 2020 --> Jul 2019 | Recruiting --> Terminated | Trial primary completion date: Dec 2020 --> Jul 2019; Business decision to stop the program.
- |||||||||| rapastinel (GLYX-13) / AbbVie
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Monotherapy: Study of Adjunctive or Monotherapy Rapastinel Treatment in Patients With Major Depressive Disorder (MDD) (clinicaltrials.gov) - Jul 18, 2019 P3, N=230, Terminated, N=690 --> 50 | Trial completion date: Dec 2020 --> Jul 2019 | Recruiting --> Terminated | Trial primary completion date: Dec 2020 --> Jul 2019; Business decision to stop the program. N=1800 --> 230 | Trial completion date: Mar 2021 --> Jul 2019 | Enrolling by invitation --> Terminated | Trial primary completion date: Feb 2021 --> Jul 2019; Business decision to stop the program
- |||||||||| rapastinel (GLYX-13) / AbbVie
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Monotherapy: Study of Monotherapy Rapastinel in the Prevention of Relapse in Patients With Major Depressive Disorder (MDD) (clinicaltrials.gov) - Jul 18, 2019 P3, N=363, Terminated, N=1800 --> 230 | Trial completion date: Mar 2021 --> Jul 2019 | Enrolling by invitation --> Terminated | Trial primary completion date: Feb 2021 --> Jul 2019; Business decision to stop the program N=1400 --> 363 | Trial completion date: Jul 2021 --> Jul 2019 | Enrolling by invitation --> Terminated | Trial primary completion date: Jul 2021 --> Jul 2019; Business decision to stop the program.
- |||||||||| buprenorphine/samidorphan (ALKS 5461) / Alkermes, rapastinel (GLYX-13) / Allergan
Journal: New medications for treatment-resistant depression: a brief review of recent developments. (Pubmed Central) - Jul 11, 2019 After a period in which it seemed as if the pharmaceutical pipeline for new antidepressants was going dry, the past decade has witnessed renewed interest, beginning with discovery of the antidepressant effects of ketamine. This article briefly highlights more recent research on ketamine and other investigational antidepressants.
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