Department of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Biophysics Program, University of Michigan, Ann Arbor, Michigan, US.
Eur J Pharm Sci. 2020 May 30;148:105326. doi: 10.1016/j.ejps.2020.105326. Epub 2020 Apr 3.
As a carbonic anhydrase inhibitor and a methylated lipophilic analogue of acetazolamide, Methazolamide has higher lipid solubility, less plasma protein binding and renal excretion, and fewer side effects, compared to acetazolamide. Methazolamide can increase systemic metabolic acidosis and sequentially improve ventilation and oxygenation level. The increased oxygenation level leads to reduced reactive oxygen species (ROS) production, relived cerebral edema, mitigated hypoxic pulmonary vasoconstriction, abrogated hypoxic fatigue, and decreased excessive erythrocytosis. In addition to the effect as a carbonic anhydrase inhibitor, methazolamide directly activates the transcription factor anti-oxidative nuclear factor-related factor 2 (Nrf2) and inhibits interleukin-1β (IL-1β) release. These pharmacological functions of methazolamide are beneficial for the prevention and treatment of high-altitude illnesses. Besides, methazolamide causes less fatigue side effects than acetazolamide does. It is also worth noting that several studies suggested that a lower dose of methazolamide has similar prophylaxis and treatment efficacy in acute mountain sickness (AMS) to a higher dose of acetazolamide. Given methazolamide's advantages over acetazolamide, methazolamide may thus represent an alternative for acetazolamide when taken for high-altitude illnesses prophylaxis and treatment. However, more in-depth clinical trials are needed to fully evaluate this efficacy of methazolamide.
甲唑胺作为碳酸酐酶抑制剂和乙酰唑胺的甲基脂溶性类似物，与乙酰唑胺相比，具有更高的脂溶性、更低的血浆蛋白结合率和肾排泄率，以及更少的副作用。甲唑胺可以增加全身代谢性酸中毒，从而依次改善通气和氧合水平。增加的氧合水平导致活性氧（ROS）产生减少，减轻脑水肿，减轻缺氧性肺血管收缩，消除缺氧性疲劳，并减少过度红细胞增多症。除了作为碳酸酐酶抑制剂的作用外，甲唑胺还直接激活转录因子抗氧化核因子相关因子 2（Nrf2）并抑制白细胞介素-1β（IL-1β）的释放。甲唑胺的这些药理作用有利于预防和治疗高山病。此外，甲唑胺引起的疲劳副作用比乙酰唑胺少。值得注意的是，几项研究表明，甲唑胺的低剂量在急性高原病（AMS）中的预防和治疗效果与乙酰唑胺的高剂量相似。鉴于甲唑胺相对于乙酰唑胺的优势，甲唑胺在预防和治疗高山病时可能是乙酰唑胺的替代品。然而，需要更多深入的临床试验来充分评估甲唑胺的疗效。
