0048 Orexin 2 receptor agonist activates pre-Bötzinger complex neurons, hypoglossal motoneurons and the genioglossus muscle in rodents
نویسندگان
چکیده
Abstract Introduction Neurons in the pre-Bötzinger complex are critical for generation of inspiratory rhythm and control activity genioglossus muscle via activation hypoglossal motoneurons. Activation causes anterior movement tongue widens upper airway. As obstructive sleep apnea (OSA) is associated with obstruction airway, this neuronal pathway may be a novel therapeutic approach. Orexins have been shown to activate these neurons by stimulation both orexin 1 receptor (OX1R) and/or 2 (OX2R). In study, we assessed effects OX2R-selective agonists on complex, motoneurons, muscle. Methods danavorexton (TAK-925) OX-201 (a tool compound longer plasma half-life than rodents) were used. Arousal investigated electroencephalogram/electromyogram recording C57BL/6J mice OX2R knockout mice. Activity motoneurons was electrophysiological rat tissues. evaluated electromyogram anesthetized rats. Results Oral administration increased wakefulness time during phase C57BL6J but not vitro analyses, danavorexton, burst frequency (EC50: 300 nM 760 nM, respectively) 610 260 respectively). Intravenous at mg/kg amplitude Conclusion enhance respiratory function through potential patients OSA if enhancement can observed non-arousal concentrations. Further preclinical clinical studies worth conducting OSA. Support (if any) This work conducted Takeda Pharmaceutical Company Limited.
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ژورنال
عنوان ژورنال: Sleep
سال: 2023
ISSN: ['0302-5128']
DOI: https://doi.org/10.1093/sleep/zsad077.0048