ArticleSleep2014
Identification of a pharmacological target for genioglossus reactivation throughout sleep.
Article in Sleep, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Are noradrenergics combined with antimuscarinics the future pharmacologic treatment for obstructive sleep apnea? A systematic review and meta-analysis of randomized controlled trials.Sleep & breathing = Schlaf & Atmung · 2024Pooled it
- The Combination of Aroxybutynin and Atomoxetine in the Treatment of Obstructive Sleep Apnea (MARIPOSA): A Randomized Controlled Trial.American journal of respiratory and critical care medicine · 2023Trial
- Combination of atomoxetine with the novel antimuscarinic aroxybutynin improves mild to moderate OSA.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2022Trial
- The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity. A Randomized, Placebo-controlled, Double-Blind Crossover Trial.American journal of respiratory and critical care medicine · 2019Trial
- Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults.Annals of the American Thoracic Society · 2017Trial
- Pharmacotherapy for Obstructive Sleep Apnea: From Pathophysiology to Emerging Treatments.Journal of clinical medicine · 2026Review
- Leptin alleviates obesity hypoventilationbioRxiv : the preprint server for biology · 2026Article
- Review
- Sleep-disordered breathing in a multiethnic cohort of preterm adolescents and adults: assessment of neonatal and subsequent risk factors.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025Article
- The Emerging Role of Pharmacotherapy in Obstructive Sleep Apnea.Journal of otorhinolaryngology, hearing and balance medicine · 2024Article
- Pharmacological interventions for the treatment of obstructive sleep apnea syndrome.Frontiers in medicine · 2024Article
- Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome.Signal transduction and targeted therapy · 2023Review
- Article
- Systemic Administration of Tempol, a Superoxide Dismutase Mimetic, Augments Upper Airway Muscle Activity in Obese Zucker Rats.Frontiers in pharmacology · 2022Article
- Obstructive sleep apnea.Handbook of clinical neurology · 2022Review
- Article
- Designer Receptors Exclusively Activated by Designer Drugs Approach to Treatment of Sleep-disordered Breathing.American journal of respiratory and critical care medicine · 2021Article
- Article
- The Role of Animal Models in Developing Pharmacotherapy for Obstructive Sleep Apnea.Journal of clinical medicine · 2019Review
- Targeting Endotypic Traits with Medications for the Pharmacological Treatment of Obstructive Sleep Apnea. A Review of the Current Literature.Journal of clinical medicine · 2019Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
STUDY
objectivesObstructive sleep apnea (OSA) is a significant public health problem caused by repeated episodes of upper airway closure that occur only during sleep. Attempts to treat OSA pharmacologically have been unsuccessful because there has not been identification of a target operating at cranial motor nuclei, blockade of which can reactivate pharyngeal muscle activity throughout sleep. Increasing potassium conductance is a common mechanism by which state-dependent neuromodulators reduce motoneuron excitability. Therefore, we aimed to determine if potassium channel blockade is an effective strategy to reactivate the pharyngeal musculature throughout sleep. DESIGN PARTICIPANTS AND
interventionsIn rats chronically instrumented for recording sleep-wake states and respiratory motor activities, we locally microperfused pharmacological agents into the hypoglossal motor pool to modulate potassium channels of three major classes: inwardly rectifying, two-pore domain, and voltage-gated. MEASUREMENTS AND
resultsMicroperfusion of the inwardly rectifying potassium channel blocker, barium, as well as the voltage-gated potassium channel blockers, tetraethylammonium and 4-aminopyridine, increased tonic and respiratory-related genioglossus activities throughout nonrapid eye movement (non-REM) and rapid eye movement (REM) sleep to 133-300% of levels present during baseline wakefulness. In contrast, microperfusion of methanandamide (TWIK-related acid-sensitive potassium [TASK] channel blocker/cannabinoid receptor agonist) activated genioglossus in wakefulness but not in sleep.
conclusionsThese findings establish proof-of-principle that targeted blockade of certain potassium channels at the hypoglossal motor pool is an effective strategy for reversing upper airway hypotonia and causing sustained reactivation of genioglossus throughout nonrapid eye movement and rapid eye movement sleep. These findings identify an important new direction for translational approaches to the pharmacological treatment of obstructive sleep apnea.
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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.