Related Experiment Video
Updated: Sep 8, 2025
Drug-Induced Sleep Endoscopy DISE with Target Controlled Infusion TCI and Bispectral Analysis in Obstructive Sleep Apnea
Published on: December 6, 2016
The Combination of Betahistine and Oxybutynin Increases Respiratory Control Sensitivity (Loop Gain) in People with
Ludovico Messineo1,2, Kelly Loffler1, Alan Chiang3
1Adelaide Institute for Sleep Health, Flinders University, Adelaide, SA, Australia.
Rationale:
There are widespread histaminergic projections throughout the brain, including hypoglossal nuclei, that modulate pharyngeal muscle tone and respiratory control. Hence, histaminergic stimulation pharmacologically may increase pharyngeal muscle tone and stabilize respiratory control (loop gain) to reduce obstructive sleep apnea (OSA) severity. Antimuscarinics also increase REM pharyngeal muscle tone in rats. Thus, a combination of histaminergic and anti-muscarinic drugs may be a novel target for OSA pharmacotherapy. However, this has not been investigated. Accordingly, we aimed to test the effects of betahistine (Beta), an H3-autoreceptor antagonist which thereby increases histamine levels, in combination with the antimuscarinic oxybutynin (Oxy), on OSA severity, OSA endotypes, polysomnography parameters and next-day sleepiness and alertness.
Methods:
Thirteen adults with OSA received either Beta-Oxy (96-5mg) or placebo according to a randomized, crossover, double-blind design, prior to polysomnography. Participants completed the Karolinska Sleep Scale and Leeds Sleep Evaluation Questionnaire and a driving simulation task to quantify next-day sleepiness and alertness. OSA endotypes were estimated through validated algorithms using polysomnography.
Results:
Compared to placebo, Beta-Oxy increased respiratory control sensitivity (loop gain) (0.52[0.24] vs 0.60[0.34], median [IQR], P = 0.021) without systematically changing OSA severity (34.4±17.2 vs 40.3±27.3 events/h, mean±SD, P = 0.124), sleep efficiency, arousal index or markers of hypoxemia. Beta-Oxy was well tolerated and did not worsen next-day sleepiness/alertness.
Conclusion:
Rather than stabilize breathing during sleep, Beta-Oxy increases loop gain, which is likely to be deleterious for most people with OSA. However, in certain conditions characterized by blunted respiratory control (eg, obesity hypoventilation syndrome), interventions to increase loop gain may be beneficial.
More Related Videos
04:59Heat-sensitive Moxibustion as a Traditional Chinese Medicine Therapy for Chronic Obstructive Pulmonary Disease Combined with Insomnia
Published on: May 30, 2025
04:53Author Spotlight: Traditional Chinese Medicine for Sleep Disorders in Acute COPD — A Safe, Cost-Effective Approach
Published on: October 18, 2024
Related Concept Videos
01:23Physiological Control of Respiration
Breathing, a seemingly passive process, is regulated by the respiratory center in the brainstem. This center coordinates the involuntary control of respirations, which means it occurs without conscious effort, ensuring a smooth and uninterrupted pattern.
Regulation of Ventilation
The body maintains ventilation by monitoring levels of carbon dioxide (CO2), oxygen (O2), and hydrogen ion concentration (pH) in the arterial blood. Among these factors, the level of CO2 plays a crucial...
01:19Respiratory Assessment: Purpose and Indications
Objectives and Importance:
The primary goal of respiratory assessment is to evaluate patients at early risk of clinical deterioration. Since respiratory distress often precedes other signs of declining health, breathing patterns and sounds become a...
01:23Mechanical Ventilation III: Noninvasive Ventilation
Noninvasive Positive-Pressure Ventilation...
01:21Sleep Apnea
The condition is more prevalent among...
01:26COPD: Management Using Bronchodilators and Corticosteroids
01:16Treatment for Pulmonary Arterial Hypertension: Oxygen Therapy for Respiratory Failure
Oxygen therapy is vital in increasing and maintaining blood oxygen levels in PAH patients. As a result, it aids in reducing fatigue,...