| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| 1g |
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| 2g |
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| 5g |
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| 25g | |||
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| Targets |
Carbonic anhydrase isozymes hCA I (Ki = 50 nM), hCA II (Ki = 14 nM), bCA IV (Ki = 36 nM). [1]
Methazolamide targets carbonic anhydrase (CA), specifically human carbonic anhydrase II, with a Ki of 14 nM. It also inhibits tumor-associated carbonic anhydrase IX (CAIX), which may result in increased cell death in hypoxic tumors. By inhibiting carbonic anhydrase in the ciliary processes of the eye, it decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. This mechanism reduces intraocular pressure and is the basis for its use in glaucoma treatment. |
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| ln Vitro |
Methazolamide is a carbonic anhydrase inhibitor with Ki of 50 nM, 14 nM and 36 nM for hCA I, hCA II and bCA IV isoforms, respectively. Methazolamide is of strength equal to acetazolamide, another carbonic anhydrase inhibitor used to treat irregular breathing disorders. However, methazolamide differs from acetazolamide in that it fails to activate Ca2+-dependent potassium channels in skeletal muscles.
Kinase Assay: Methazolamide is a carbonic anhydrase inhibitor with Ki of 50 nM, 14 nM and 36 nM for hCA I, hCA II and bCA IV isoforms, respectively. In vitro, Methazolamide is a potent inhibitor of human carbonic anhydrase II with a Ki of 14 nM. It also inhibits tumor-associated carbonic anhydrase IX (CAIX), which may result in increased cell death in hypoxic tumors. The compound exhibits neuroprotective effects by inhibiting neuronal apoptosis. Its activity has been characterized in enzyme assays using purified CA II, and its ability to reduce intraocular pressure has been demonstrated in cell-based models of ocular fluid secretion. These in vitro studies confirm its mechanism as a carbonic anhydrase inhibitor. |
| ln Vivo |
Methazolamide does not impair respiratory work performance in anesthetized rabbits.
In vivo, Methazolamide is an orally active intraocular pressure-lowering agent. It reduces intraocular pressure elevations associated with glaucoma and other ocular disorders. It has been used clinically for the treatment of open-angle glaucoma and acute angle-closure glaucoma. The compound also exhibits neuroprotective properties in vivo and has been investigated for cerebrovascular diseases such as subarachnoid hemorrhage. Its ability to reduce intraocular pressure has been established in clinical settings, making it a well-characterized therapeutic agent. |
| Enzyme Assay |
The carbonic anhydrase inhibitory activity was determined using a stopped-flow variant of the Pocker and Stone spectrophotometric method, which measures the esterase activity of the enzyme with 4-nitrophenyl acetate as substrate. The assay was performed using a stopped-flow instrument. [1]
Non-cellular enzyme assays for Methazolamide typically involve measuring its inhibition of carbonic anhydrase (CA) activity. These assays use purified CA II enzyme and a spectrophotometric or fluorometric substrate, such as 4-nitrophenyl acetate, to measure the rate of enzymatic reaction in the presence of varying concentrations of Methazolamide. The compound's ability to inhibit CA is assessed by determining the inhibition constant (Ki). Such assays are essential for characterizing its mechanism as a carbonic anhydrase inhibitor and for quantifying its potency. |
| Cell Assay |
In vitro cell-based assays for Methazolamide are conducted using ocular cell lines, such as ciliary epithelial cells, to assess its effects on fluid secretion and intraocular pressure. Cells are treated with the compound, and changes in bicarbonate ion transport, sodium flux, and fluid secretion are measured. Additionally, neuroprotection assays can be performed using neuronal cell cultures to evaluate its ability to inhibit apoptosis. These assays are crucial for confirming its mechanism of action at the cellular level and for identifying its therapeutic potential in glaucoma and other ocular disorders.
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| Animal Protocol |
In vivo animal studies for Methazolamide are typically conducted in animal models of glaucoma or elevated intraocular pressure to evaluate its efficacy. The compound is administered orally or intraperitoneally, and intraocular pressure is measured using tonometry. Its effects on aqueous humor secretion and optic nerve protection are assessed. These studies are essential for validating its in vivo efficacy as an intraocular pressure-lowering agent and for establishing appropriate dosing regimens.
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| ADME/Pharmacokinetics |
Methazolamide is an orally active compound with a molecular weight of 236.27 g/mol. It is administered orally for the treatment of glaucoma. Its pharmacokinetic properties are well-characterized, and it is known to be well-absorbed from the gastrointestinal tract. It is metabolized in the liver and excreted by the kidneys. Its half-life and other pharmacokinetic parameters are available from clinical studies. It is a prescription drug for the treatment of glaucoma and other ocular disorders.
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| Toxicity/Toxicokinetics |
Methazolamide has an established safety profile from its clinical use. It is generally well-tolerated, but common side effects include gastrointestinal disturbances, fatigue, and paresthesia. It can also cause metabolic acidosis due to its carbonic anhydrase inhibition. As with all carbonic anhydrase inhibitors, it should be used with caution in patients with renal or hepatic impairment. Comprehensive toxicological data are available from its clinical use. Methazolamide is an approved drug for the treatment of glaucoma.
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| References |
Bioorg Med Chem Lett.2003;13(5):841-5;Am J Physiol Regul Integr Comp Physiol.2009;297(3):R648-54.
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| Additional Infomation |
Methazolamide belongs to the thiadiazole sulfonamide class of drugs. It is a carbonic anhydrase inhibitor and is used as a diuretic and to treat glaucoma. See also: Mezalazole (note moved to).
Methazolamide is a standard carbonic anhydrase inhibitor (CAI) used as a reference compound in this study. It belongs to the aromatic/heterocyclic sulfonamide class of CAIs, which have been used as drugs for over 45 years. [1] Methazolamide (L584601) is a sulfonamide derivative and a potent carbonic anhydrase inhibitor with a Ki of 14 nM for human carbonic anhydrase II. It is an orally active intraocular pressure-lowering agent used to treat glaucoma. It also inhibits tumor-associated carbonic anhydrase IX (CAIX) and exhibits neuroprotective properties. Methazolamide is an approved drug for the treatment of open-angle glaucoma and acute angle-closure glaucoma. |
| Molecular Formula |
C5H8N4O3S2
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| Molecular Weight |
236.27
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| Exact Mass |
236.003
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| CAS # |
554-57-4
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| Related CAS # |
Methazolamide-d6;1795142-30-1
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| PubChem CID |
4100
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| Appearance |
White to off-white solid powder
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| Density |
1.8±0.1 g/cm3
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| Boiling Point |
402.0±28.0 °C at 760 mmHg
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| Melting Point |
208ºC (dec.)
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| Flash Point |
196.9±24.0 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.737
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| LogP |
0.13
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
14
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| Complexity |
419
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(/N=C1SC(S(=O)(N)=O)=NN/1C)=O
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| InChi Key |
FLOSMHQXBMRNHR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C5H8N4O3S2/c1-3(10)7-4-9(2)8-5(13-4)14(6,11)12/h1-2H3,(H2,6,11,12)
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| Chemical Name |
N-(3-methyl-5-sulfamoyl-1,3,4-thiadiazol-2-ylidene)acetamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 47 mg/mL (198.9 mM)
Water: 1 mg/mL (Insoluble) Ethanol: 3 mg/mL (12.7 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.58 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (10.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2324 mL | 21.1622 mL | 42.3245 mL | |
| 5 mM | 0.8465 mL | 4.2324 mL | 8.4649 mL | |
| 10 mM | 0.4232 mL | 2.1162 mL | 4.2324 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05498103 | Recruiting | Drug: Methazolamide 25 MG Drug: Methazolamide 50 MG |
Glaucoma, Open-Angle | University of Colorado, Denver | February 17, 2023 | Phase 4 |
| NCT06312800 | Withdrawn | Drug: Placebo Drug: Methazolamide |
Essential Tremor | Henry Ford Health System | March 2016 | Phase 2 |
| NCT01587027 | Completed Has Results | Drug: Aminophylline Drug: Methazolamide |
Mountain Sickness | Poudre Valley Health System | December 2011 | Phase 1 |
| NCT05575180 | Completed | Drug: Acetazolamide 250Mg Tab Drug: Methazolamide Pill |
High Altitude Effects | University of Waterloo | August 11, 2023 | Phase 4 |
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