title: Desipramine Increases Genioglossus Activity and Reduces Upper Airway Collapsibility during Non-REM Sleep in Healthy Subjects.
abstract: Obstructive sleep apnea is a state-dependent disease. One of the key factors that triggers upper airway collapse is decreased pharyngeal dilator muscle activity during sleep. To date, there have not been effective methods to reverse pharyngeal hypotonia pharmacologically in sleeping humans.
  
  
  
  We tested the hypothesis that administration of desipramine 200 mg prevents the state-related reduction in genioglossus activity that occurs during sleep and thereby decreases pharyngeal collapsibility.
  
  
  
  We conducted a placebo-controlled, double-blind, crossover trial with 10 healthy participants. Participants received active treatment or placebo in randomized order 2 hours before sleep in the physiology laboratory.
  
  
  
  Genioglossus activity during wakefulness and sleep, genioglossus muscle responsiveness to negative epiglottic pressure, and upper airway collapsibility during passive and active conditions were compared between on- and off-drug states. Desipramine abolished the normal reduction of genioglossus activity from wakefulness to non-REM sleep that occurred on the placebo night. Specifically, tonic (median, 96% [86-120] vs. 75% [50-92] wakefulness; P = 0.01) but not phasic genioglossus activity was higher with desipramine compared with placebo. Upper airway collapsibility was also reduced with desipramine compared with placebo (-10.0 cm H2O [-15.2 to -5.8] vs. -8.1 cm H2O [-10.4 to -6.3]; P = 0.037).
  
  
  
  Desipramine reduces the state-related drop in tonic genioglossus muscle activity that occurs from wakefulness to non-REM sleep and reduces airway collapsibility. These data provide a rationale for a new pharmacologic therapy for obstructive sleep apnea. Clinical trial registered with www.clinicaltrials.gov (NCT02428478).
authors.affiliation: 1 Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Luigi
authors.initials: L
authors.lastname: Taranto-Montemurro
authors.affiliation: 1 Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|2 Sleep and Circadian Medicine Laboratory and.|3 Monash institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Edwards
authors.affiliation: 1 Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|4 Department of Allergy, Immunology, and Respiratory Medicine, The Alfred and.|5 Central Clinical School, Monash University, Melbourne, Victoria, Australia; and.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Sands
authors.affiliation: 1 Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Melania
authors.initials: M
authors.lastname: Marques
authors.affiliation: 6 Neuroscience Research Australia, University of New South Wales, Randwick, Sydney, New South Wales, Australia.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eckert
authors.affiliation: 1 Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: David P
authors.initials: DP
authors.lastname: White
authors.affiliation: 1 Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wellman
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D045422:Continuous Positive Airway Pressure / Q000379:methods; D018592:Cross-Over Studies; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology*; D004576:Electromyography / Q000187:drug effects; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D010609:Pharyngeal Muscles / Q000187:drug effects* / Q000502:physiology; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D003891:Desipramine
keywords: norepinephrine reuptake inhibitor; pharmacological treatment; pharyngeal dilator muscle; sleep-disordered breathing