Carbonic anhydrase inhibition and chemoreflex control of breathing: A litmus test for methazolamide as a viable alternative to acetazolamide
Bibliographic record
Abstract
Carbonic anhydrase inhibitors are used in clinical, experimental and environmental settings to regulate acid-base balance in the blood and tissues.Acetazolamide is a carbonic anhydrase inhibitor routinely prescribed in the treatment of pulmonary disorders, glaucoma and sleep-disordered breathing.It is also commonly used prophylactically and therapeutically in acute mountain sickness.In the context of high altitude, acetazolamide is used to accelerate the acclimatization process by inhibiting renal bicarbonate reabsorption, increasing its secretion, thereby inducing a relative systemic metabolic acidosis.Resting ventilation is increased via chemoreceptor stimulation, and resting oxygenation is improved.However, in both animal and human studies, administration of acetazolamide has been shown to cause respiratory muscle dysfunction (Dominelli et al., 2018;Kiwull-Schöne, Teppema, & Kiwull, 2001), which potentially limits its usage.Methazolamide, a sister carbonic anhydrase inhibitor with much higher membrane permeability than acetazolamide, does not cause respiratory muscle impairment (Dominelli et al., 2018;Kiwull-Schöne, Li, Kiwull, & Teppema, 2009) and, as such, might be an effective and suitable alternative.The benign effect of methazolamide on respiratory muscle function is established, whereas its effects on chemoreflex control of breathing are unknown, but are important to establish if consideration is to be given to the potential use of methazolamide as a viable alternative treatment option in clinical and environmental settings.In this issue of Experimental Physiology, Teppema et al. (2020) compare the effects of acetazolamide and methazolamide on chemoreflex control of breathing in young, healthy, male participants, by way of assessment of ventilatory sensitivity to independent and
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".