{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:58:30Z","timestamp":1792151910713,"version":"4.4.0"},"reference-count":63,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/501100000038","name":"Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en G\u00e9nie du Canada)","doi-asserted-by":"publisher","award":["05643"],"award-info":[{"award-number":["05643"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000245","name":"Michael Smith Foundation for Health Research (MSFHR)","doi-asserted-by":"publisher","award":["16806"],"award-info":[{"award-number":["16806"]}],"id":[{"id":"10.13039\/501100000245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation (Fondation canadienne pour l'innovation)","doi-asserted-by":"publisher","award":["32158"],"award-info":[{"award-number":["32158"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:p>Acetazolamide, a carbonic anhydrase (CA) inhibitor used clinically and to prevent acute mountain sickness, worsens skeletal muscle fatigue in animals and humans. In animals, methazolamide, a methylated analog of acetazolamide and an equally potent CA inhibitor, reportedly exacerbates fatigue less than acetazolamide. Accordingly, we sought to determine, in humans, if methazolamide would attenuate diaphragm and dorsiflexor fatigue compared with acetazolamide. Healthy men (dorsiflexor: n = 12; diaphragm: n = 7) performed fatiguing exercise on three occasions, after ingesting acetazolamide (250 mg three times a day) and then in random order, methazolamide (100 mg twice a day) or placebo for 48 h. For both muscles, subjects exercised at a fixed intensity until exhaustion on acetazolamide, with subsequent iso-time and -workload trials. Diaphragm exercise was performed using a threshold-loading device, while dorsiflexor exercise was isometric. Neuromuscular function was determined pre- and postexercise by potentiated transdiaphragmatic twitch pressure and dorsiflexor torque in response to stimulation of the phrenic and fibular nerve, respectively. Diaphragm contractility 3\u201310 min postexercise was impaired more for acetazolamide than methazolamide or placebo (82\u2009\u00b1\u200910, 87\u2009\u00b1\u20099, and 91\u2009\u00b1\u20098% of pre-exercise value; P &lt; 0.05). Similarly, dorsiflexor fatigue was greater for acetazolamide than methazolamide (mean twitch torque of 61\u2009\u00b1\u200911 vs. 57\u2009\u00b1\u200913% of baseline, P &lt; 0.05). In normoxia, methazolamide leads to less neuromuscular fatigue than acetazolamide, indicating a possible benefit for clinical use or in the prophylaxis of acute mountain sickness.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY Acetazolamide, a carbonic anhydrase inhibitor, may worsen diaphragm and locomotor muscle fatigue after exercise; whereas, in animals, methazolamide does not impair diaphragm function. Compared with both methazolamide and the placebo, acetazolamide significantly compromised dorsiflexor function at rest and after exhaustive exercise. Similarly, diaphragm function was most compromised on acetazolamide followed by methazolamide and placebo. Methazolamide may be preferable over acetazolamide for clinical use and altitude illness prophylaxis to avoid skeletal muscle dysfunction.<\/jats:p>","DOI":"10.1152\/japplphysiol.00256.2018","type":"journal-article","created":{"date-parts":[[2018,5,31]],"date-time":"2018-05-31T16:16:36Z","timestamp":1527783396000},"page":"770-779","source":"Crossref","is-referenced-by-count":22,"title":["Effect of acetazolamide and methazolamide on diaphragm and dorsiflexor fatigue: a randomized controlled trial"],"prefix":"10.1152","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5575-4043","authenticated-orcid":false,"given":"Paolo B.","family":"Dominelli","sequence":"first","affiliation":[{"name":"Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J.","family":"McNeil","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler D.","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy J. 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