ArticleFrontiers in neuroscience2014
LSN2424100: a novel, potent orexin-2 receptor antagonist with selectivity over orexin-1 receptors and activity in an animal model predictive of antidepressant-like efficacy.
Article in Frontiers in neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Suvorexant for Primary Insomnia: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.PloS one · 2015Pooled it
- Efficacy and Safety of Seltorexant as Adjunctive Therapy in Major Depressive Disorder: A Phase 2b, Randomized, Placebo-Controlled, Adaptive Dose-Finding Study.The international journal of neuropsychopharmacology · 2021Trial
- New Antidepressant Development in the Treatment of Depression.Advances in experimental medicine and biology · 2026Review
- Orexin receptors: possible therapeutic targets for psychiatric disorders.Psychopharmacology · 2025Review
- Pyrazole derivatives as selective orexin-2 receptor antagonists (2-SORA): synthesis, structure-activity-relationship, and sleep-promoting properties in rats.RSC medicinal chemistry · 2024Article
- Orexin Receptor Antagonists as Adjunct Drugs for the Treatment of Depression: A Mini Meta-Analysis.Noro psikiyatri arsivi · 2024Review
- Orexin Signaling: A Complex, Multifaceted Process.Frontiers in cellular neuroscience · 2022Review
- Orexin receptors in GtoPdb v.2021.3.IUPHAR/BPS guide to pharmacology CITE · 2021Article
- Synthesis and biological activity evaluation of azacycloheptane sulfonamide derivatives as potential orexin receptor antagonists.RSC advances · 2020Article
- Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders.Neuroscience bulletin · 2020Review
- Therapeutics development for addiction: Orexin-1 receptor antagonists.Brain research · 2020Review
- Hypnotics with novel modes of action.British journal of clinical pharmacology · 2020Review
- An alerting structure: human orexin receptor 1.Nature structural & molecular biology · 2016Article
- Orexin/hypocretin based pharmacotherapies for the treatment of addiction: DORA or SORA?CNS drugs · 2014Review
- Opportunities and perspectives for developing orexin receptor antagonists.Frontiers in neuroscience · 2014Article
- Orexin-1 and orexin-2 receptor antagonists reduce ethanol self-administration in high-drinking rodent models.Frontiers in neuroscience · 2014Article
- Orexin OXCurrent topics in behavioral neurosciencesReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We describe a novel, potent and selective orexin-2 (OX2)/hypocretin-2 receptor antagonist with in vivo activity in an animal model predictive of antidepressant-like efficacy. N-biphenyl-2-yl-4-fluoro-N-(1H-imidazol-2-ylmethyl) benzenesulfonamide HCl (LSN2424100) binds with high affinity to recombinant human OX2 receptors (Ki = 4.5 nM), and selectivity over OX1 receptors (Ki = 393 nM). LSN2424100 inhibited OXA-stimulated intracellular calcium release in HEK293 cells expressing human and rat OX2 receptors (Kb = 0.44 and 0.83 nM, respectively) preferentially over cells expressing human and rat OX1 (Kb = 90 and 175 nM, respectively). LSN2424100 exhibits good exposure in Sprague-Dawley rats after IP, but not PO, administration of a 30 mg/kg dose (AUC0-6 h = 1300 and 269 ng(*)h/mL, respectively). After IP administration in rats and mice, LSN2424100 produces dose-dependent antidepressant-like activity in the delayed-reinforcement of low-rate (DRL) assay, a model predictive of antidepressant-like efficacy. Efficacy in the DRL model was lost in mice lacking OX2, but not OX1 receptors, confirming OX2-specific activity. Importantly, antidepressant-like efficacy of the tricyclic antidepressant, imipramine, was maintained in both OX1 and OX2 receptor knock-out mice. In conclusion, the novel OX2 receptor antagonist, LSN2424100, is a valuable tool compound that can be used to explore the role of OX2 receptor-mediated signaling in mood disorders.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.