ArticleDepression and anxiety2015
OREXIN 1 AND 2 RECEPTOR INVOLVEMENT IN CO2 -INDUCED PANIC-ASSOCIATED BEHAVIOR AND AUTONOMIC RESPONSES.
Article in Depression and anxiety, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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.
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Who cites it
38 citing papers in PubMed, 64 citations in OpenAlex.
- Functional Plasticity of Orexin/Hypocretin Neurons Balances Stress States.Biological psychiatry · 2026Review
- Depression and Anxiety as Comorbidities in Chronic Obstructive Pulmonary Disease: A Comprehensive Narrative Review.Healthcare (Basel, Switzerland) · 2025Review
- Early life stress and hormonal status influence orexin-1 receptor expression in structures regulating cardiorespiratory responses to COExperimental physiology · 2025Article
- Orexin receptors: possible therapeutic targets for psychiatric disorders.Psychopharmacology · 2025Review
- Fear attenuation collaborations to optimize translation.Behavioral neuroscience · 2024Article
- Identification of a novel perifornical-hypothalamic-area-projecting serotonergic system that inhibits innate panic and conditioned fear responses.Translational psychiatry · 2024Article
- Anxiolytic-like effects of the dual orexin receptor antagonist daridorexant in rats.Neuroscience applied · 2024Article
- The role of the orexin system in the neurobiology of anxiety disorders: Potential for a novel treatment target.Neuroscience applied · 2024Review
- Orexin Receptor Antagonists as Adjunct Drugs for the Treatment of Depression: A Mini Meta-Analysis.Noro psikiyatri arsivi · 2024Review
- Characteristics of Seltorexant-Innovative Agent Targeting Orexin System for the Treatment of Depression and Anxiety.Molecules (Basel, Switzerland) · 2023Review
- Dual Cannabinoid and Orexin Regulation of Anhedonic Behaviour Caused by Prolonged Restraint Stress.Brain sciences · 2023Article
- Dual Orexin Receptor Antagonist Attenuates Increases in IOP, ICP, and Translaminar Pressure Difference After Stimulation of the Hypothalamus in Rats.Investigative ophthalmology & visual science · 2022Article
- Neurobiology of the Orexin System and Its Potential Role in the Regulation of Hedonic Tone.Brain sciences · 2022Review
- Discovery of Arylsulfonamides as Dual Orexin Receptor Agonists.Journal of medicinal chemistry · 2021Article
- Individual differences in rat sensitivity to CO2.PloS one · 2021Article
- Orexin receptors in GtoPdb v.2021.3.IUPHAR/BPS guide to pharmacology CITE · 2021Article
- Experimental Drugs for Panic Disorder: An Updated Systematic Review.Journal of experimental pharmacology · 2021Review
- Hypocretin (Orexin) Replacement Therapies.Medicine in drug discovery · 2020Article
- Disruption of estradiol regulation of orexin neurons: a novel mechanism in excessive ventilatory response to COTranslational psychiatry · 2020Article
- Substituted Azabicyclo[2.2.1]heptanes as Selective Orexin-1 Antagonists: Discovery of JNJ-54717793.ACS medicinal chemistry letters · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe neuropeptides orexin A and B play a role in reward and feeding and are critical for arousal. However, it was not initially appreciated that most prepro-orexin synthesizing neurons are almost exclusively concentrated in the perifornical hypothalamus, which when stimulated elicits panic-associated behavior and cardiovascular responses in rodents and self-reported "panic attacks" and "fear of dying" in humans. More recent studies support a role for the orexin system in coordinating an integrative stress response. For instance, orexin neurons are highly reactive to anxiogenic stimuli, are hyperactive in anxiety pathology, and have strong projections to anxiety and panic-associated circuitry. Although the two cognate orexin receptors are colocalized in many brain regions, the orexin 2 receptor (OX2R) most robustly maps to the histaminergic wake-promoting region, while the orexin 1 receptor (OX1R) distribution is more exclusive and dense in anxiety and panic circuitry regions, such as the locus ceruleus. Overall, this suggests that OX1Rs play a critical role in mobilizing anxiety and panic responses.
methodsHere, we used a CO2 -panic provocation model to screen a dual OX1/2R antagonist (DORA-12) to globally inhibit orexin activity, then a highly selective OX1R antagonist (SORA1, Compound 56) or OX2R antagonist (SORA2, JnJ10397049) to assess OX1R and OX2R involvement.
resultsAll compounds except the SORA2 attenuated CO2 -induced anxiety-like behaviors, and all but the SORA2 and DORA attenuated CO2 -induced cardiovascular responses.
conclusionsSORA1s may represent a novel method of treating anxiety disorders, with no apparent sedative effects that were present with a benzodiazepine.
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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.