{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:49:00Z","timestamp":1790034540468,"version":"4.0.1"},"reference-count":65,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:00:00Z","timestamp":1495670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MT\u201015563"],"award-info":[{"award-number":["MT\u201015563"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL102321"],"award-info":[{"award-number":["R01 HL102321"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL 128658"],"award-info":[{"award-number":["R01 HL 128658"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL 095491"],"award-info":[{"award-number":["P01 HL 095491"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL 094307"],"award-info":[{"award-number":["P01 HL 094307"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>\n<jats:styled-content style=\"fixed-case\">ABSTRACT<\/jats:styled-content>\n<\/jats:title><jats:p>There is currently no pharmacotherapy for obstructive sleep apnoea (<jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>) but there is no principled a priori reason why there should not be one. This review identifies a rational decision\u2010making strategy with the necessary logical underpinnings that any reasonable approach would be expected to navigate to develop a viable pharmacotherapy for <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>. The process first involves phenotyping an individual to quantify and characterize the critical predisposing factor(s) to their <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> pathogenesis and identify, a priori, if the patient is likely to benefit from a pharmacotherapy that targets those factors. We then identify rational strategies to manipulate those critical predisposing factor(s), and the barriers that have to be overcome for success of any <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> pharmacotherapy. A new analysis then identifies candidate drug targets to manipulate the upper airway motor circuitry for <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> pharmacotherapy. The first conclusion is that there are two general pharmacological approaches for <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> treatment that are of the most potential benefit and are practically realistic, one being fairly intuitive but the second perhaps less so. The second conclusion is that after identifying the critical physiological obstacles to <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> pharmacotherapy, there are current therapeutic targets of high interest for future development. The final analysis provides a tabulated resource of \u2018druggable\u2019 targets that are relatively restricted to the circuitry controlling the upper airway musculature, with these candidate targets being of high priority for screening and further study. We also emphasize that a pharmacotherapy may not cure <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> <jats:italic>per se<\/jats:italic>, but may still be a useful adjunct to improve the effectiveness of, and adherence to, other treatment mainstays.<\/jats:p>","DOI":"10.1111\/resp.13079","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T17:22:11Z","timestamp":1495732931000},"page":"861-873","source":"Crossref","is-referenced-by-count":59,"title":["A resource of potential drug targets and strategic decision\u2010making for obstructive sleep apnoea pharmacotherapy"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5593-2548","authenticated-orcid":false,"given":"Richard L.","family":"Horner","sequence":"first","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Department of Physiology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4746-6353","authenticated-orcid":false,"given":"Kevin P.","family":"Grace","sequence":"additional","affiliation":[{"name":"Institute of Medical Science University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wellman","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2109080"},{"key":"e_1_2_9_3_1","first-page":"55","volume-title":"Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem","author":"Institute of Medicine","year":"2006"},{"key":"e_1_2_9_4_1","first-page":"137","volume-title":"Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem","author":"Institute of Medicine","year":"2006"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/147.4.887"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4160-6645-3.00107-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201109-1614OC"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1308659"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599815616618"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c110064"},{"key":"e_1_2_9_11_1","first-page":"961","article-title":"An integrative model of physiological traits can be used to predict obstructive sleep apnea and response to non positive airway pressure therapy","volume":"38","author":"Owens RL","year":"2015","journal-title":"Sleep"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00747.2012"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00282.2006"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00043.2008"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.12913"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.245159"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201303-0448OC"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201601-0099OC"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201404-0718OC"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2014.07.002"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01358.2010"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00062914"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.4.9706067"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.223925"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20100588"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.2390"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00649.2013"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.90408.2008"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201408-399OC"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.5622"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00312.2011"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00067607"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.5.9812007"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2009.01699.x"},{"key":"e_1_2_9_35_1","first-page":"CD003002","article-title":"Drug therapy for obstructive sleep apnoea in adults","author":"Smith I","year":"2006","journal-title":"Cochrane Database Syst. Rev."},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200464130-00001"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543780902877674"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2011.590473"},{"key":"e_1_2_9_39_1","first-page":"Cd003002","article-title":"Drug therapy for obstructive sleep apnoea in adults","author":"Mason M","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200605-597OC"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201209-1654OC"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.07.011"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.3304"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00823-2016"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201511-2172OC"},{"key":"e_1_2_9_46_1","unstructured":"WellmanDA. Effect of atomoxetine and oxybutynin on phenotype traits and OSA severity.ClinicalTrials.govIdentifier: NCT02908529."},{"key":"e_1_2_9_47_1","unstructured":"WellmanDA. The effect of desipramine on genioglossus muscle activity during sleep in healthy control subjects.ClinicalTrials.govIdentifier: NCT02428478."},{"key":"e_1_2_9_48_1","unstructured":"WellmanDA. The effect of dalfampridine (4\u2010aminopyridine) on genioglossus muscle activity during wakefulness and sleep in healthy control subjects.ClinicalTrials.govIdentifier: NCT02656160."},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00531.2013"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00032.2011"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/19.10.827"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05453"},{"key":"e_1_2_9_53_1","unstructured":"Allen Mouse Brain Atlas 2004. [Accessed 4 Jan 2017.] Available from URL:http:\/\/mouse.brain\u2010map.org\/"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903570305"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(97)00028-3"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.230"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2199"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1179"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-11-04096.1998"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep45860"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44392"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.07.014"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4501-04.2005"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.08.026"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0274-14.2014"}],"container-title":["Respirology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fresp.13079","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/resp.13079","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T04:23:25Z","timestamp":1696047805000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/resp.13079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,25]]},"references-count":65,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1111\/resp.13079"],"URL":"https:\/\/doi.org\/10.1111\/resp.13079","archive":["Portico"],"relation":{},"ISSN":["1323-7799","1440-1843"],"issn-type":[{"value":"1323-7799","type":"print"},{"value":"1440-1843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,25]]}}}