Influence of methazolamide on the human control of breathing: A comparison to acetazolamide.

Abstract

NEW FINDINGS:

What is the central question of this study? Acetazolamide and methazolamide both reduce hypoxic pulmonary vasoconstriction equally, but methazolamide does not impair skeletal muscle function. The effect of methazolamide on respiratory control in humans is not yet known. What is the main finding and its importance? Similar to acetazolamide after chronic oral administration, methazolamide causes a metabolic acidosis and shifts the ventilatory CO2 response curve leftwards without reducing O2 sensitivity. The change in ventilation over the change in log PO2 provides a more accurate measure of hypoxic sensitivity than the change in ventilation over the change in arterial oxyhaemoglobin saturation.

ABSTRACT:

Acetazolamide is used to prevent/treat acute mountain sickness and both central and obstructive sleep apnoea. Methazolamide, like acetazolamide, reduces hypoxic pulmonary vasoconstriction, but has fewer side-effects, including less impairment of skeletal muscle function. Given that the effects of methazolamide on respiratory control in humans are unknown, we compared the effects of oral methazolamide and acetazolamide on ventilatory control and determined the ventilation-log  PO2 relationship in humans. In a double-blind, placebo-controlled, randomized cross-over design, we studied the effects of acetazolamide (250 mg three times daily), methazolamide (100 mg twice daily) and placebo in 14 young male subjects who were exposed to 7 min of normoxic hypercapnia and to three levels of eucapnia and hypercapnic hypoxia. With placebo, methazolamide and acetazolamide, the CO2 sensitivities were 2.39 ± 1.29, 3.27 ± 1.82 and 2.62 ± 1.79 l min-1  mmHg-1 (n.s.) and estimated apnoeic thresholds 32 ± 3, 28 ± 3 and 26 ± 3 mmHg, respectively (P < 0.001, placebo versus methazolamide and acetazolamide). The relationship between ventilation ( V̇I ) and log  PO2 (using arterialized venous PO2 in hypoxia) was linear, and neither agent influenced the relationship between hypoxic sensitivity ( ΔV̇I/ΔlogPO2 ) and arterial [H+ ]. Using ΔV̇I/ΔlogPO2 rather than Δ V̇I /Δ arterial oxyhaemoglobin saturation enables a more accurate estimation of oxygenation and ventilatory control in metabolic acidosis/alkalosis when right- or leftward shifts of the oxyhaemoglobin saturation curve occur. Given that acetazolamide and methazolamide have similar effects on ventilatory control, methazolamide might be preferred for indications requiring the use of a carbonic anhydrase inhibitor, avoiding some of the negative side-effects of acetazolamide.

• Authors: Luc J Teppema, Lindsey M Boulet, Heather K Hackett, Paolo B Dominelli, William S Cheyne, Giulio S Dominelli, Erik R Swenson, Glen E Foster
• Journal: Experimental physiology (Exp Physiol) Vol. 105 Issue 2 Pg. 293-301 (02 2020) ISSN: 1469-445X [Electronic] England
• PMID: 31595565 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.

Chemical References

• Carbonic Anhydrase Inhibitors
• Acetazolamide
• Methazolamide

Topics

• Acetazolamide (pharmacology)
• Adult
• Carbonic Anhydrase Inhibitors (pharmacology)
• Cross-Over Studies
• Double-Blind Method
• Humans
• Male
• Methazolamide (pharmacology)
• Pulmonary Ventilation (drug effects, physiology)
• Respiration (drug effects)
• Young Adult