{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:29:25Z","timestamp":1776918565455,"version":"3.51.2"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"am","delay-in-days":343,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T00:00:00Z","timestamp":1590451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["N66001\u201010\u2010C\u20102134"],"award-info":[{"award-number":["N66001\u201010\u2010C\u20102134"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Does the combination of methazolamide and theophylline reduce symptoms of acute mountain sickness (AMS) and improve aerobic performance in acute hypobaric hypoxia?<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>The oral combination of methazolamide (100\u00a0BID) and theophylline (300\u00a0BID) improved arterial oxygen saturation but did not reduce symptoms of AMS and impaired aerobic performance. We do not recommend this combination of drugs for prophylaxis against the acute negative effects of hypobaric hypoxia.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>A limited number of small studies have suggested that methazolamide and theophylline can independently reduce symptoms of acute mountain sickness (AMS) and, if taken together, can improve aerobic exercise performance in normobaric hypoxia. We performed a randomized, double\u2010blind, placebo\u2010controlled, cross\u2010over study to determine if the combination of oral methazolamide and theophylline could provide prophylaxis against AMS and improve aerobic performance in hypobaric hypoxia (\u223c4875\u00a0m). Volunteers with histories of AMS were screened at low altitude (1650\u00a0m) and started combined methazolamide (100\u00a0mg BID) and theophylline (300\u00a0mg BID) treatment, or placebo, 72\u00a0h prior to decompression. Baseline AMS (Lake Louise Questionnaire), blood (haemoglobin, haematocrit), cognitive function, ventilatory and pulse oximetry (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/eph12756-math-0001.png\" xlink:title=\"urn:x-wiley:09580670:media:eph12756:eph12756-math-0001\"\/>) measures were assessed at low altitude and repeated between 4 and 10\u00a0h of exposure to hypobaric hypoxia (<jats:italic>P<\/jats:italic><jats:sub>B\u00a0<\/jats:sub>=\u00a0425\u00a0mmHg). Aerobic exercise performance was assessed during a 12.5\u00a0km cycling time trial (TT) after 4\u00a0h of hypobaric hypoxia. Subjects repeated all experimental procedures after a 3\u2010week washout period. Differences between drug and placebo trials were evaluated using repeated measures ANOVA (\u03b1\u00a0=\u00a00.05). The drugs improved resting <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/eph12756-math-0002.png\" xlink:title=\"urn:x-wiley:09580670:media:eph12756:eph12756-math-0002\"\/> by \u223c4% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), but did not affect the incidence or severity of AMS or cognitive function scores relative to placebo. Subjects\u2019 performance on the 12.5\u00a0km TT was \u223c3% worse when taking the drugs (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). The combination of methazolamide and theophylline in the prescribed dosages is not recommended for use at high altitude as it appears to have no measurable effect on AMS and can impair aerobic performance.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep088461","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T08:28:36Z","timestamp":1588580916000},"page":"117-125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Combined methazolamide and theophylline improves oxygen saturation but not exercise performance or altitude illness in acute hypobaric hypoxia"],"prefix":"10.1113","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9719-7660","authenticated-orcid":false,"given":"Andrew W.","family":"Subudhi","sequence":"first","affiliation":[{"name":"Altitude Research Center University of Colorado Anschutz Medical Campus  Aurora CO USA"},{"name":"Department of Human Physiology and Nutrition University of Colorado Colorado Springs  Colorado Springs CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oghenero","family":"Evero","sequence":"additional","affiliation":[{"name":"Altitude Research Center University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Reitinger","sequence":"additional","affiliation":[{"name":"Altitude Research Center University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Davis","sequence":"additional","affiliation":[{"name":"Altitude Research Center University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Gronewold","sequence":"additional","affiliation":[{"name":"Altitude Research Center University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Altitude Research Center University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja Jameson","family":"Van\u2010Houten","sequence":"additional","affiliation":[{"name":"Altitude Research Center University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C.","family":"Roach","sequence":"additional","affiliation":[{"name":"Altitude Research Center University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1249\/00003677-197400020-00006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00509.2018"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00655.2019"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wem.2014.04.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00256.2018"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.03.00113102"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.2000.15a22.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)92385-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20050233"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00746.2001"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107123450206"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1972133349"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.120949"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1708-8305.2008.00228.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.7205\/MILMED-D-12-00438"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01572.2005"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.05.024"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wem.2019.04.006"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.07-1417"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1972.222.6.1361"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1967.47.4.595"},{"issue":"8","key":"e_1_2_9_23_1","first-page":"730","article-title":"The pharmacology of methazolamide in relation to the treatment of glaucoma","volume":"16","author":"Maren T. 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