- |||||||||| 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;
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
- |||||||||| Nectiv (traxoprodil) / Pfizer
Dopamine depletion alters GluN2-subunits contribution to NMDA receptor currents in striatal projection neurons (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_11522;
In this study, we used MPX-004, CP101606, and NAB-14...These results suggest that dopamine loss leads to a reorganization of NMDAR subunits in i-SPNs characterized by an increased expression of GluN2B- and GluN2D-subunits, but not GluN2A-subunits and that these changes may underlie the altered activity of these neurons. Comparison of these results to findings in d-SPNs will provide further insights into the pathophysiology of striatal dysfunction in PD.
- |||||||||| ifenprodil tartrate / Chiba University Hospital, Nectiv (traxoprodil) / Pfizer
Journal: Binding Affinity and Mechanisms of Potential Antidepressants Targeting Human NMDA Receptors. (Pubmed Central) - Jun 14, 2023
We further compared S-ketamine and its chiral molecule, R-ketamine, and found that R-ketamine had a stronger binding capacity to the NMDA receptor. This study provides a computational reference for the treatment of depression targeting NMDA receptors, and the proposed results will provide potential strategies for further antidepressant development and is a useful resource for the future discovery of fast-acting antidepressant candidates.
- |||||||||| Nectiv (traxoprodil) / Pfizer
Journal: Antidepressant-like effect of CP-101,606: Evidence of mTOR pathway activation. (Pubmed Central) - Mar 2, 2023
Our results demonstrate that CP-101,606 produces antidepressant effects in CUMS mice, which may be mediated by mTOR signaling cascade upregulation. Our findings suggest the possible utility of CP-101,606 as a treatment for depression.
- |||||||||| Nectiv (traxoprodil) / Pfizer
Review, Journal: N-methyl-D-aspartate receptor antagonists in improving cognitive deficits following traumatic brain injury: a systematic review. (Pubmed Central) - Sep 20, 2022
Although some benefits were observed, there are still some concerns regarding the efficacy and safety of NMDAR antagonists in improving post-TBI cognitive deficits. Further research is required to examine whether (i) these agents, notably amantadine, could accelerate cognitive improvement and shorten the hospital stay, (ii) these agents affect different cognitive domains/subdomains in the same direction, (iii) an optimal therapeutic time window exists, (iv) a member of this drug class can be proved to be effective without interfering in non-excitotoxic actions of glutamate, (v) they can be more effective as part of combination therapies or in particular subgroups of patients with TBI.
- |||||||||| Review: Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents. (Pubmed Central) - Jul 20, 2022
Sestrin modulators, cholinergic receptor modulators, or onabotulinumtoxinA have also been investigated for potential antidepressant activity. In conclusion, there is hope for new treatments in uni- and bipolar depression, as it became clear, after almost 7 decades of monoamine-modulating antidepressants, that new pathogenetic pathways should be targeted to increase the response rate in this population.
- |||||||||| dextromethorphan / Generic mfg.
Journal: Ouabain inhibitor rostafuroxin attenuates dextromethorphan-induced manic potential. (Pubmed Central) - Jan 28, 2022
Further, ROSTA and traxoprodil also failed to enhance PKCδ depletion effect, suggesting that PKCδ is a critical target for the anti-manic potential of ROSTA or GluN2B antagonism. Our results suggest that ROSTA inhibits DM-induced manic potential by attenuating ERK/Akt activation, GluN2B/PKCδ signalings, and Nrf2-dependent system.
- |||||||||| 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., Nectiv (traxoprodil) / Pfizer
Journal: Blockade of GluN2B-containing NMDA receptors reduces short-term brain damage induced by early-life status epilepticus. (Pubmed Central) - Jan 11, 2020
Fifteen minutes after pilocarpine administration, animals received i.p. injections of saline solution (0.9% NaCl; SE + SAL group), ketamine (a non-selective and noncompetitive NMDAR antagonist; 25 mg/kg; SE + KET), CI-1041 (a GluN2B-containing NMDAR antagonist; 10 mg/kg; SE + CI group) or CP-101,606 (a NMDAR antagonist with great selectivity for NMDAR composed by GluN1/GluN2B diheteromers; 10 mg/kg; SE + CP group)...However, GluN2B-containing NMDAR blockade by CI-1041 reduced neurodegeneration and Iba1/ED1 double-labeling in hippocampus and amygdala similar to the reduction observed for SE + KET group. Our results indicate that GluN2B-containing NMDAR are involved in SE-induced neurodegeneration and microglial recruitment and activation, and suggest that stopping epileptic activity is not a condition required to prevent short-term brain damage in young animals.
- |||||||||| Nectiv (traxoprodil) / Pfizer
Preclinical, Journal: Mapping the central effects of (±)-ketamine and traxoprodil using pharmacological magnetic resonance imaging in awake rats. (Pubmed Central) - Oct 27, 2019
Traxoprodil at 5 mg/kg and 15 mg/kg produced a dose-dependent pharmacological magnetic resonance imaging signal in rat forebrain regions with both doses achieving >80% N-methyl-D-aspartate receptor subtype 2B occupancy determined by ex vivo [3H]Ro 25-6981 binding. The middle dose of traxoprodil (5 mg/kg) generated region-specific activations in medial prefrontal cortex, ventral orbital cortex, and anterior cingulate cortex whereas the high dose (15 mg/kg) produced a widespread pharmacological magnetic resonance imaging response in both cortical and subcortical brain regions which was similar to that produced by (±)-ketamine (3 mg/kg, intravenous).
- |||||||||| 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.
- |||||||||| Valdoxan (agomelatine) / Servier, Novartis, Edronax (reboxetine) / Pfizer, Latuda (lurasidone oral) / Sumitomo Dainippon
Clinical, Review, Journal: The emergence of new antidepressants for clinical use: Agomelatine paradox versus other novel agents. (Pubmed Central) - Jun 21, 2019
...The emerging antidepressants are: selective monoamine oxidase inhibitors (MAOIs) such as bifemelane, pirlindole, toloxatone, selegiline, rasagiline and safinamide; serotonin-norepinephrine reuptake inhibitors (SNRIs) such as ansofaxine, nefopam and levomilnacipran; norepinephrine reuptake inhibitors (NRIs) such as Reboxetine, viloxazine, teniloxazine (also known as sulfoxazine or sufoxazine), and atomoxetine; Vilazodone (a serotonin 5-HT autoreceptor partial agonist with serotonin reuptake inhibition [SPARI]); Vortioxetine (a serotonin receptors antagonist with serotonin reuptake inhibition [SARI]); atypical antipsychotics such as olanzapine, quetiapine, risperidone, lurasidone, aripiprazole and brexpiprazole; N-methyl-d-aspartate (NMDA)-glutamatergic neurotransmission system blockers such as ketamine, CP-101,606 (traxoprodil), GLYX-13 (rapastinel), NRX-1074 (Apimostinel) and Riluzole...receptors antagonist [MASSA]) remains a paradoxical agent that doesn't fit into any of the currently available classes of antidepressant agents and its pharmacological properties also deemed it unfit and inappropriate to be classified into another separate novel class of antidepressants contrary to the reports published in previous reference literatures. Lastly, this review remarkably advocates for the incorporation of the atypical antipsychotics and NMDA-glutamatergic ionoceptor blockers as new member classes of the antidepressant agents because of their clinically significant roles in the management of depression disorders.
- |||||||||| Journal: Glutamatergic Modulators in Depression. (Pubmed Central) - Jun 7, 2019
These results have prompted the repurposing or development of other glutamatergic modulators, both as monotherapy or adjunctive to other therapies. Here, we highlight the evidence supporting the antidepressant effects of various glutamatergic modulators, including (1) broad glutamatergic modulators (ketamine, esketamine, dextromethorphan, dextromethorphan-quinidine [Nuedexta], AVP-786, nitrous oxide [N2O], AZD6765), (2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists (CP-101,606/traxoprodil, MK-0657 [CERC-301]), (3) glycine-site partial agonists (D-cycloserine, GLYX-13, sarcosine, AV-101), and (4) metabotropic glutamate receptor modulators (AZD2066, RO4917523/basimglurant, JNJ40411813/ADX71149, R04995819 [RG1578]).
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