Effect of acetazolamide and methazolamide on diaphragm and dorsiflexor fatigue: a randomized controlled trial

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 th...

Full description

Saved in:
Bibliographic Details
Published in:Journal of applied physiology (1985) 2018-09, Vol.125 (3), p.770-779
Main Authors: Dominelli, Paolo B, McNeil, Chris J, Vermeulen, Tyler D, Stuckless, Troy J R, Brown, Courtney V, Dominelli, Giulio S, Swenson, Erik R, Teppema, Lucas J, Foster, Glen E
Format: Article
Language:English
Subjects:
Acetazolamide
Animals
Carbonic anhydrase
Carbonic anhydrases
Clinical trials
Diaphragm
Effects
Exhaustion
Fatigue
Inhibitors
Isometric exercise
Muscle contraction
Muscles
Muscular fatigue
Prescription drugs
Prophylaxis
Respiratory system
Skeletal muscle
Torque
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 3-10 min postexercise was impaired more for acetazolamide than methazolamide or placebo (82 ± 10, 87 ± 9, and 91 ± 8% of pre-exercise value; P < 0.05). Similarly, dorsiflexor fatigue was greater for acetazolamide than methazolamide (mean twitch torque of 61 ± 11 vs. 57 ± 13% of baseline, P < 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. NEW & 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.
ISSN:8750-7587
1522-1601
DOI:10.1152/japplphysiol.00256.2018