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Methazolamide in high-altitude illnesses.

Hui Lu1, Huaqun Zhang2, Yuanying Jiang1

  • 1Department of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
|April 7, 2020
PubMed
Summary

Methazolamide, a carbonic anhydrase inhibitor, offers an alternative to acetazolamide for high-altitude illnesses due to fewer side effects and comparable efficacy. Further clinical trials are recommended for comprehensive evaluation.

Keywords:
Excessive erythrocytosisFatigueHigh-altitude illnessesHypoxic pulmonary vasoconstrictionHypoxic ventilatory responseMethazolamideOxidative stress

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Area of Science:

  • Pharmacology
  • Altitude Medicine
  • Respiratory Physiology

Background:

  • Methazolamide is a methylated lipophilic analogue of acetazolamide with enhanced properties.
  • It functions as a carbonic anhydrase inhibitor, increasing systemic metabolic acidosis.
  • This leads to improved ventilation and oxygenation levels.

Purpose of the Study:

  • To evaluate methazolamide's efficacy and safety for high-altitude illnesses.
  • To compare methazolamide with acetazolamide in prophylaxis and treatment.
  • To explore methazolamide's pharmacological mechanisms beyond carbonic anhydrase inhibition.

Main Methods:

  • Review of existing literature on methazolamide and acetazolamide.
  • Analysis of pharmacological effects including lipid solubility, protein binding, and side effect profiles.
  • Assessment of clinical outcomes in high-altitude illness prophylaxis and treatment.

Main Results:

  • Methazolamide exhibits higher lipid solubility and lower plasma protein binding than acetazolamide.
  • It reduces reactive oxygen species, cerebral edema, and hypoxic pulmonary vasoconstriction.
  • Methazolamide activates Nrf2 and inhibits IL-1β, with fewer fatigue side effects and comparable efficacy to acetazolamide at lower doses for acute mountain sickness.

Conclusions:

  • Methazolamide presents a promising alternative to acetazolamide for high-altitude illness prevention and treatment.
  • Its distinct pharmacological actions contribute to its therapeutic benefits.
  • Further extensive clinical trials are necessary to fully establish its efficacy and optimal use.