Methazolamide (L584601) is a sulfonamide derivative used as a carbonic anhydrase inhibitor with a Ki of 14 nM for human carbonic anhydrase II[3]. Methazolamide is an intraocular pressure-lowering drug that is used in the treatment of glaucoma and other ophthalmologic abnormalities[4]. Methazolamide can increase systemic metabolic acidosis and sequentially improve ventilation and oxygenation level. 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. Methazolamide may thus represent an alternative for acetazolamide when taken for high-altitude illnesses prophylaxis and treatment[5]. Methazolamide exhibits dose-dependent efficacy for the treatment of excessive erythrocytosis induced by long-term hypoxia[6].
Methazolamide/醋甲唑胺 细胞实验
Cell Line
Concentration
Treated Time
Description
References
hCMEC/D3 microvascular endothelial cells
100 μM and 300 μM
45 minutes
MTZ and ATZ prevented Aβ40-Q22-induced mitochondrial membrane depolarization and H2O2 generation, and inhibited apoptosis.
Aging Cell. 2018 Aug;17(4):e12787
SH-SY5Y neuronal cells
100 μM and 300 μM
45 minutes
MTZ and ATZ prevented Aβ42-induced mitochondrial membrane depolarization and H2O2 generation, and inhibited apoptosis.
Aging Cell. 2018 Aug;17(4):e12787
Primary rat cortical neurons
300 μM
24 hours
To evaluate the protective effect of methazolamide on Aβ42-induced mitochondrial dysfunction, results showed methazolamide restored basal and maximal respiration as well as ATP production levels
Alzheimers Res Ther. 2020 Jan 13;12(1):13
SH-SY5Y neuroblastoma cells
300 μM
24 hours
To evaluate the protective effect of methazolamide on Aβ42-induced mitochondrial dysfunction, results showed methazolamide restored basal and maximal respiration as well as ATP production levels
Alzheimers Res Ther. 2020 Jan 13;12(1):13
Vero E6 cells
100 μM
6 hours
To evaluate the effect of methazolamide on SARS-CoV-2 infection, results showed that methazolamide dramatically reduced the viral RNA in the cell culture medium by up to 89.1%–99.9%.
Cell Metab. 2022 Mar 1;34(3):424-440. e7
Human umbilical vein endothelial cells (HUVECs)
25 μM
16 hours
To evaluate the effect of methazolamide on ACE2 enzymatic activity, results showed that methazolamide significantly elevated the enzymatic activity of ACE2.
Cell Metab. 2022 Mar 1;34(3):424-440. e7
SH-SY5Y neuroblastoma cells
30 μM
12 hours
To evaluate the effect of methazolamide on intracellular tau clearance, results showed methazolamide slowed the accumulation of GFP-tau-P301L and promoted tau secretion.
Nat Chem Biol. 2025 Apr;21(4):577-587
Human CD34+ progenitor cells
30 µg/ml
14 days
To evaluate the effect of MZ on human mast cell development, results showed MZ significantly reduced mast cell numbers.
J Exp Med. 2016 Aug 22;213(9):1663-73
BM-derived macrophages
30 µg/ml
5 days
To evaluate the effect of MZ on macrophage development, results showed MZ had no effect on macrophage development.
J Exp Med. 2016 Aug 22;213(9):1663-73
BM-derived basophils
30 µg/ml
7 days
To evaluate the effect of MZ on basophil development, results showed MZ increased basophil percentages but decreased total numbers.
J Exp Med. 2016 Aug 22;213(9):1663-73
BM-derived mast cells
30 µg/ml
7 days
To evaluate the effect of MZ on mast cell development, results showed MZ significantly reduced mast cell populations.
J Exp Med. 2016 Aug 22;213(9):1663-73
Normal Human Astrocytes
10 μM Aβ42 or 50 μM Aβ40-Q22
24 hours
MTZ significantly reduced Aβ42 and Aβ40-Q22-induced DNA fragmentation, indicating its anti-apoptotic effect.
Neurobiol Dis. 2016 Feb;86:29-40
Glioma cells (M059K)
10 μM Aβ42 or 50 μM Aβ40-Q22
3 days
MTZ significantly reduced Aβ42 and Aβ40-Q22-induced DNA fragmentation, indicating its anti-apoptotic effect.
Neurobiol Dis. 2016 Feb;86:29-40
Human neuroblastoma cells (SH-SY5Y)
10 μM Aβ42 or 50 μM Aβ40-Q22
24 hours
MTZ significantly reduced Aβ42 and Aβ40-Q22-induced DNA fragmentation, indicating its anti-apoptotic effect.
Neurobiol Dis. 2016 Feb;86:29-40
Methazolamide/醋甲唑胺 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
High-fat-diet-induced insulin-resistant mice
Gavage
100 mg/kg
Once daily for 4 weeks
To evaluate the effect of methazolamide on metabolic defects in SARS-CoV-2-infected mice, results showed that methazolamide significantly improved insulin resistance and dyslipidemia.
Cell Metab. 2022 Mar 1;34(3):424-440. e7
TgSwDI mice
Model of Alzheimer’s disease and cerebral amyloid angiopathy
Dietary administration
20mg/kg/day
Once daily for 8 months or 4 months
To evaluate the effects of CAIs on cognitive function and Aβ pathology in TgSwDI mice. Results showed that CAIs improved spatial memory, reduced cerebral Aβ deposition, and decreased caspase-3 activation.
Alzheimers Dement. 2023 Nov;19(11):5048-5073
Mice
T. spiralis infection model
Intraperitoneal injection
2-3 mg
Daily for 10-11 days
To evaluate the effect of MZ on T. spiralis infection-induced mast cell responses, results showed MZ significantly reduced mast cell responses and inflammation.
J Exp Med. 2016 Aug 22;213(9):1663-73
Kunming mice
Hypoxia tolerance model
Intraperitoneal injection
100 mg/kg
Single dose, lasting 1 hour
Evaluate the effect of methazolamide on hypoxia tolerance in mice, results showed that methazolamide significantly improved hypoxia tolerance in mice
Mil Med Res. 2018 Sep 30;5(1):33
Mice
Tg4510 transgenic mouse model
Subcutaneous osmotic minipumps
10, 20, 50 mg/kg/day
Once daily for 28 days
To evaluate the effect of methazolamide on tau protein levels and cognitive function, results showed methazolamide reduced total and phosphorylated tau levels and improved cognitive function.
Nat Chem Biol. 2025 Apr;21(4):577-587
Mice
Tg-SwDI genetic mouse model
Oral
20 mg/kg/day
Once daily for 6 months
Prevent molecular adaptations and retain glutamatergic synapse proteins significantly closer to wild-type levels
Alzheimers Dement. 2025 Apr;21(4):e70122
C57BL/6 mice
Aβ40-Q22 intrahippocampal injection model
Intraperitoneal injection
20 mg/kg
Single injection, observed for 4 hours
MTZ reduced Aβ-induced caspase 3 activation and neuronal loss by inhibiting mitochondrial H2O2 production.
Neurobiol Dis. 2016 Feb;86:29-40
Mouse
Aβ-induced neurodegeneration model
10 mg/kg
MTZ reduced Aβ-induced caspase activation and neuronal death.
United States, Florida
... 展开 >>
Bascom Palmer Eye Institute - University of Miami
Recruiting
Miami, Florida, United States, 33136
Contact: Marlene Perez, RC 305-482-4309 marlene.perez@med.miami.edu
Contact: Shiva Roghaee, RA 305 482 4309 sxr935@med.miami.edu
Principal Investigator: Vittorio Porciatti, DSc
Sub-Investigator: John J McSoley, OD
Sub-Investigator: Luis E Vazquez, MD,PhD
Sub-Investigator: Steven J Gedde, MD
Sub-Investigator: Pedro F Monsalve, RA
Sub-Investigator: Maja Kostic, PhD 收起 <<
United States, Florida
... 展开 >>
Bascom Palmer Eye Institute - University of Miami
Recruiting
Miami, Florida, United States, 33136
Contact: Marlene Perez, RC 305-482-4309 marlene.perez@med.miami.edu
Contact: Shiva Roghaee, RA 305 482 4309 sxr935@med.miami.edu
Principal Investigator: Vittorio Porciatti, DSc
Sub-Investigator: John J McSoley, OD
Sub-Investigator: Luis E Vazquez, MD,PhD
Sub-Investigator: Steven J Gedde, MD
Sub-Investigator: Pedro F Monsalve, RA
Sub-Investigator: Maja Kostic, PhD 收起 <<
Physiological Function in Low ... 展开 >>Oxygen Environment 收起 <<
Phase 1
Phase 2
Completed
-
United States, Colorado
... 展开 >>
Colorado State University, Dept. of Health and Exercise Science
Fort Collins, Colorado, United States, 80523-1582 收起 <<
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