Methazolamide Plus Aminophylline Abrogates Hypoxia-Mediated Endurance Exercise Impairment.

Abstract

In hypoxia, endurance exercise performance is diminished; pharmacotherapy may abrogate this performance deficit. Based on positive outcomes in preclinical trials, we hypothesized that oral administration of methazolamide, a carbonic anhydrase inhibitor, aminophylline, a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor, and/or methazolamide combined with aminophylline would attenuate hypoxia-mediated decrements in endurance exercise performance in humans. Fifteen healthy males (26 ± 5 years, body-mass index: 24.9 ± 1.6 kg/m(2); mean ± SD) were randomly assigned to one of four treatments: placebo (n = 9), methazolamide (250 mg; n = 10), aminophylline (400 mg; n = 9), or methazolamide (250 mg) with aminophylline (400 mg; n = 8). On two separate occasions, the first in normoxia (FIO2 = 0.21) and the second in hypoxia (FIO2 = 0.15), participants sat for 4.5 hours before completing a standardized exercise bout (30 minutes, stationary cycling, 100 W), followed by a 12.5-km time trial. The magnitude of time trial performance decrement in hypoxia versus normoxia did not differ between placebo (+3.0 ± 2.7 minutes), methazolamide (+1.4 ± 1.7 minutes), and aminophylline (+1.8 ± 1.2 minutes), all with p > 0.09; however, the performance decrement in hypoxia versus normoxia with methazolamide combined with aminophylline was less than placebo (+0.6 ± 1.5 minutes; p = 0.01). This improvement may have been partially mediated by increased SpO2 in hypoxia with methazolamide combined with aminophylline compared with placebo (73% ± 3% vs. 79% ± 6%; p < 0.02). In conclusion, coadministration of methazolamide and aminophylline may promote endurance exercise performance during a sojourn at high altitude.

• Authors: Rebecca L Scalzo, Scott E Binns, Anna L Klochak, Gregory R Giordano, Hunter L R Paris, Kyle J Sevits, Joseph W Beals, Laurie M Biela, Dennis G Larson, Gary J Luckasen, David Irwin, Thies Schroeder, Karyn L Hamilton, Christopher Bell
• Journal: High altitude medicine & biology (High Alt Med Biol) Vol. 16 Issue 4 Pg. 331-42 (Dec 2015) ISSN: 1557-8682 [Electronic] United States
• PMID: 26680684 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Aminophylline
• Methazolamide

Topics

• Adult
• Altitude
• Aminophylline (administration & dosage)
• Drug Therapy, Combination
• Exercise (physiology)
• Exercise Test (drug effects)
• Healthy Volunteers
• Humans
• Hypoxia (drug therapy, physiopathology)
• Male
• Methazolamide (administration & dosage)
• Physical Endurance (drug effects)
• Young Adult