{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:07:16Z","timestamp":1793383636324,"version":"4.5.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The reduction in upper airway muscle activity from wakefulness to sleep plays a key role in the development of obstructive sleep apnea. Potassium (K+) channels have been recently identified as the downstream mechanisms through which hypoglossal motoneuron membrane excitability is reduced both in non-rapid eye movement (NREM) sleep and REM sleep. In animal models, the administration of 4-aminopyridine (4-AP), a voltage-gated K+ channel blocker, increased genioglossus activity during wakefulness and across all sleep stages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We tested the hypothesis that administration of a single dose of 4-AP 10 mg extended release would increase genioglossus activity (electromyography of the genioglossus muscle [EMGGG]) during wakefulness and sleep, and thereby decrease pharyngeal collapsibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a randomized controlled crossover proof-of-concept trial in 10 healthy participants. Participants received active treatment or placebo in randomized order 3 hours before bedtime in the physiology laboratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EMGGG during wakefulness and NREM sleep and upper airway collapsibility measured during NREM sleep were unchanged between placebo and 4-AP nights. Tonic but not phasic EMGGG during REM sleep was higher on the 4-AP night when measured as a percentage of maximal voluntary activation (median [interquartile range] 0.3 [0.5] on placebo vs. 0.8 [1.9] %max on 4 AP; P\u2009=\u20090.04), but not when measured in \u03bcV or as a percentage of wakefulness value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A single dose of 4-AP 10 mg extended release showed only a small increase in tonic EMGGG during REM sleep in this group of healthy subjects. We speculate that a higher dose of 4-AP may further increase EMGGG. However, given the potentially severe, dose-related adverse effects of this drug, including seizures, the administration of 4-AP does not appear to be an effective strategy to increase genioglossus activity during sleep in humans.<\/jats:p>\n                    <jats:p>Clinical Trial registered with clinicaltrials.gov (NCT02656160).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1513\/annalsats.201701-006oc","type":"journal-article","created":{"date-parts":[[2017,4,7]],"date-time":"2017-04-07T11:41:04Z","timestamp":1491565264000},"page":"1177-1183","source":"Crossref","is-referenced-by-count":7,"title":["Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults"],"prefix":"10.1093","volume":"14","author":[{"given":"Luigi","family":"Taranto-Montemurro","sequence":"first","affiliation":[{"name":"Department of Medicine and Department of Neurology, Division of Sleep and Circadian Disorders, Brigham & Women\u2019s Hospital & Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Sands","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Neurology, Division of Sleep and Circadian Disorders, Brigham & Women\u2019s Hospital & Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Allergy, Immunology and Respiratory Medicine and Central Clinical School, The Alfred and Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Azarbarzin","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Neurology, Division of Sleep and Circadian Disorders, Brigham & Women\u2019s Hospital & Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"Marques","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Neurology, Division of Sleep and Circadian Disorders, Brigham & Women\u2019s Hospital & Harvard Medical School, Boston, Massachusetts"},{"name":"Pulmonary Division, Heart Institute, Hospital das Cl\u00ednicas, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila M.","family":"de Melo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Neurology, Division of Sleep and Circadian Disorders, Brigham & Women\u2019s Hospital & Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Psychobiology, Federal University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley A.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Sleep and Circadian Medicine Laboratory, Department of Physiology, Monash University, Melbourne, Victoria, Australia"},{"name":"School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny J.","family":"Eckert","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia and the University of New South Wales, Randwick, Sydney, Australia; 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