title: 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.affiliation: 1 Department of Health and Exercise Science, Colorado State University , Fort Collins, Colorado.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Scalzo
authors.affiliation: 1 Department of Health and Exercise Science, Colorado State University , Fort Collins, Colorado.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Binns
authors.affiliation: 1 Department of Health and Exercise Science, Colorado State University , Fort Collins, Colorado.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Klochak
authors.affiliation: 1 Department of Health and Exercise Science, Colorado State University , Fort Collins, Colorado.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Giordano
authors.affiliation: 1 Department of Health and Exercise Science, Colorado State University , Fort Collins, Colorado.
authors.forename: Hunter L R
authors.initials: HL
authors.lastname: Paris
authors.affiliation: 1 Department of Health and Exercise Science, Colorado State University , Fort Collins, Colorado.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Sevits
authors.affiliation: 1 Department of Health and Exercise Science, Colorado State University , Fort Collins, Colorado.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Beals
authors.affiliation: 1 Department of Health and Exercise Science, Colorado State University , Fort Collins, Colorado.
authors.forename: Laurie M
authors.initials: LM
authors.lastname: Biela
authors.affiliation: 2 Heart Center of the Rockies, University of Colorado Health , Fort Collins, Colorado.
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Larson
authors.affiliation: 2 Heart Center of the Rockies, University of Colorado Health , Fort Collins, Colorado.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Luckasen
authors.affiliation: 3 University of Colorado-Denver , Denver, Colorado.
authors.forename: David
authors.initials: D
authors.lastname: Irwin
authors.affiliation: 4 Department of Physical Chemistry, University of Mainz , Mainz, Germany .
authors.forename: Thies
authors.initials: T
authors.lastname: Schroeder
authors.affiliation: 1 Department of Health and Exercise Science, Colorado State University , Fort Collins, Colorado.
authors.forename: Karyn L
authors.initials: KL
authors.lastname: Hamilton
authors.affiliation: 1 Department of Health and Exercise Science, Colorado State University , Fort Collins, Colorado.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bell
mesh_terms: D000328:Adult; D000531:Altitude; D000628:Aminophylline / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test / Q000187:drug effects; D064368:Healthy Volunteers; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008704:Methazolamide / Q000008:administration & dosage*; D010807:Physical Endurance / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000628:Aminophylline; D008704:Methazolamide
keywords: high-altitude; methazolamide; theophylline