Details
Stereochemistry | ACHIRAL |
Molecular Formula | C5H8N4O3S2 |
Molecular Weight | 236.272 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1N=C(S\C1=N\C(C)=O)S(N)(=O)=O
InChI
InChIKey=FLOSMHQXBMRNHR-QPJJXVBHSA-N
InChI=1S/C5H8N4O3S2/c1-3(10)7-4-9(2)8-5(13-4)14(6,11)12/h1-2H3,(H2,6,11,12)/b7-4+
Molecular Formula | C5H8N4O3S2 |
Molecular Weight | 236.272 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
DescriptionSources: http://www.drugbank.ca/drugs/DB00703Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/pro/methazolamide.html
Sources: http://www.drugbank.ca/drugs/DB00703
Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/pro/methazolamide.html
Methazolamide is topical carbonic anhydrase inhibitor. Methazolamide is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to beta-blockers. Methazolamide is a sulfonamide derivative; however, it does not have any clinically significant antimicrobial properties. Although methazolamide achieves a high concentration in the cerebrospinal fluid, it is not-considered an effective anticonvulsant. Methazolamide has a weak and transient diuretic effect, therefore use results in an increase in urinary volume, with excretion of sodium, potassium and chloride. Methazolamide is a potent inhibitor of carbonic anhydrase. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. Methazolamide is used for treatment of chronic open-angle glaucoma and acute angle-closure glaucoma.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23965175 |
50.0 nM [Ki] | ||
Target ID: CHEMBL205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23965175 |
14.0 nM [Ki] | ||
Target ID: CHEMBL3594 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23965175 |
27.0 nM [Ki] | ||
Target ID: CHEMBL3242 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23965175 |
3.4 nM [Ki] | ||
Target ID: CHEMBL2326 Sources: http://www.drugbank.ca/drugs/DB00703 |
2.1 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Methazolamide Approved Useindicated in the treatment of ocular conditions where lowering intraocular pressure is likely to be of therapeutic benefit, such as chronic open-angle glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where lowering the intraocular pressure is desired before surgery. Launch Date7.4131197E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.5 μg/mL |
25 mg 2 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
METHAZOLAMIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
5.1 μg/mL |
50 mg 2 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
METHAZOLAMIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
10.7 μg/mL |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
METHAZOLAMIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1130 μg × min/mL |
25 mg 2 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
METHAZOLAMIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
2571 μg × min/mL |
50 mg 2 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
METHAZOLAMIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
5418 μg × min/mL |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
METHAZOLAMIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14 h |
steady-state, oral |
METHAZOLAMIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
45% |
25 mg 2 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
METHAZOLAMIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
100 mg 3 times / day multiple, oral Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 67.5 years n = 24 Health Status: unhealthy Condition: Glaucoma Age Group: 67.5 years Sex: M+F Population Size: 24 Sources: |
Disc. AE: Loss of energy, Fatigue... AEs leading to discontinuation/dose reduction: Loss of energy (2 patients) Sources: Fatigue (2 patients) Lethargy (2 patients) |
50 mg 2 times / day multiple, oral Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Co-administed with:: aspirin(high concentration) Sources: |
unhealthy |
Disc. AE: Anorexia, Tachypnea... AEs leading to discontinuation/dose reduction: Anorexia Sources: Tachypnea Lethargy Coma |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Fatigue | 2 patients Disc. AE |
100 mg 3 times / day multiple, oral Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 67.5 years n = 24 Health Status: unhealthy Condition: Glaucoma Age Group: 67.5 years Sex: M+F Population Size: 24 Sources: |
Lethargy | 2 patients Disc. AE |
100 mg 3 times / day multiple, oral Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 67.5 years n = 24 Health Status: unhealthy Condition: Glaucoma Age Group: 67.5 years Sex: M+F Population Size: 24 Sources: |
Loss of energy | 2 patients Disc. AE |
100 mg 3 times / day multiple, oral Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 67.5 years n = 24 Health Status: unhealthy Condition: Glaucoma Age Group: 67.5 years Sex: M+F Population Size: 24 Sources: |
Anorexia | Disc. AE | 50 mg 2 times / day multiple, oral Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Co-administed with:: aspirin(high concentration) Sources: |
unhealthy |
Coma | Disc. AE | 50 mg 2 times / day multiple, oral Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Co-administed with:: aspirin(high concentration) Sources: |
unhealthy |
Lethargy | Disc. AE | 50 mg 2 times / day multiple, oral Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Co-administed with:: aspirin(high concentration) Sources: |
unhealthy |
Tachypnea | Disc. AE | 50 mg 2 times / day multiple, oral Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Co-administed with:: aspirin(high concentration) Sources: |
unhealthy |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://dmd.aspetjournals.org/content/38/2/347 Page: 348.0 |
no |
PubMed
Title | Date | PubMed |
---|---|---|
Treatment of essential tremor with methazolamide. | 1991 Oct |
|
Carbonic anhydrase inhibitors. Inhibition of the prokariotic beta and gamma-class enzymes from Archaea with sulfonamides. | 2004 Dec 20 |
|
Carbonic anhydrase inhibitors. Design of anticonvulsant sulfonamides incorporating indane moieties. | 2004 Dec 6 |
|
Carbonic anhydrase inhibitors. Inhibition of cytosolic isozyme XIII with aromatic and heterocyclic sulfonamides: a novel target for the drug design. | 2004 Jul 16 |
|
Benzolamide is not a membrane-impermeant carbonic anhydrase inhibitor. | 2004 Jun |
|
Carbonic anhydrase inhibitors: the first QSAR study on inhibition of tumor-associated isoenzyme IX with aromatic and heterocyclic sulfonamides. | 2004 Jun 21 |
|
Alkalization of larval mosquito midgut and the role of carbonic anhydrase in different species of mosquitoes. | 2004 Mar |
|
Theoretical study of gas-phase acidity, pKa, lipophilicity, and solubility of some biologically active sulfonamides. | 2004 Oct 15 |
|
Measuring drug concentrations using pulsatile microdialysis: theory and method development in vitro. | 2005 Apr 11 |
|
Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides. | 2005 Feb 15 |
|
Carbonic anhydrase inhibitors. Inhibition of the human cytosolic isozyme VII with aromatic and heterocyclic sulfonamides. | 2005 Feb 15 |
|
Carbonic anhydrase inhibitors. Inhibition of the transmembrane isozyme XII with sulfonamides-a new target for the design of antitumor and antiglaucoma drugs? | 2005 Feb 15 |
|
Stimulation of renal sulfate secretion by metabolic acidosis requires Na+/H+ exchange induction and carbonic anhydrase. | 2005 Jul |
|
Mechanism of augmented duodenal HCO(3)(-) secretion after elevation of luminal CO(2). | 2005 Mar |
|
Functional interaction of carbonic anhydrase and chloride/bicarbonate exchange in human platelets. | 2005 Nov |
|
Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides. | 2005 Sep 1 |
|
Carbonic anhydrase inhibitors: cloning and sulfonamide inhibition studies of a carboxyterminal truncated alpha-carbonic anhydrase from Helicobacter pylori. | 2006 Apr 15 |
|
Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels. | 2006 Jan |
|
Epithelial carbonic anhydrases facilitate PCO2 and pH regulation in rat duodenal mucosa. | 2006 Jun 15 |
|
Mirtazapine in the treatment of essential tremor: an open-label, observer-blind study. | 2006 Mar |
|
Carbonic anhydrase inhibitors: DNA cloning and inhibition studies of the alpha-carbonic anhydrase from Helicobacter pylori, a new target for developing sulfonamide and sulfamate gastric drugs. | 2006 Mar 23 |
|
Topical dorzolamide for the treatment of cystoid macular edema in patients with retinitis pigmentosa. | 2006 May |
|
The development of topically acting carbonic anhydrase inhibitors as anti-glaucoma agents. | 2007 |
|
Statement on high-altitude illnesses. An Advisory Committee Statement (ACS). | 2007 Apr 1 |
|
Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. | 2007 Dec 1 |
|
Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy. | 2007 Dec 3 |
|
Carbonic anhydrase inhibitors. DNA cloning, characterization, and inhibition studies of the human secretory isoform VI, a new target for sulfonamide and sulfamate inhibitors. | 2007 Jan 25 |
|
Topical inhibition of nasal carbonic anhydrase affects the CO2 detection threshold in rats. | 2007 Mar |
|
The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. | 2008 |
|
The alpha and beta classes carbonic anhydrases from Helicobacter pylori as novel drug targets. | 2008 |
|
CO2 chemosensing in rat oesophagus. | 2008 Dec |
|
Rational use of the fixed combination of dorzolamide - timolol in the management of raised intraocular pressure and glaucoma. | 2008 Jun |
|
Pharmacological impact on loop gain properties to prevent irregular breathing. | 2008 Mar |
|
Recent advances in pharmacotherapy of glaucoma. | 2008 Oct |
|
Inhibitors of cytochrome c release with therapeutic potential for Huntington's disease. | 2008 Sep 17 |
|
Acetazolamide reversibly inhibits water conduction by aquaporin-4. | 2009 Apr |
|
Studies on bicarbonate transporters and carbonic anhydrase in porcine nonpigmented ciliary epithelium. | 2009 Apr |
|
QSAR studies for the inhibition of the transmembrane carbonic anhydrase isozyme XIV with sulfonamides using PRECLAV software. | 2009 Apr |
|
Molecular cloning, characterization, and inhibition studies of the Rv1284 beta-carbonic anhydrase from Mycobacterium tuberculosis with sulfonamides and a sulfamate. | 2009 Apr 23 |
|
Functional coupling of the downregulated in adenoma Cl-/base exchanger DRA and the apical Na+/H+ exchangers NHE2 and NHE3. | 2009 Feb |
|
Carbonic anhydrase inhibitors: inhibition of the beta-class enzyme from the yeast Saccharomyces cerevisiae with sulfonamides and sulfamates. | 2009 Feb 1 |
|
Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. | 2009 Feb 1 |
|
Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties. | 2009 Feb 17 |
|
Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides. | 2009 Jul 1 |
|
Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. | 2009 Jul 15 |
|
Titration calorimetry standards and the precision of isothermal titration calorimetry data. | 2009 Jun 18 |
|
Methazolamide and melatonin inhibit mitochondrial cytochrome C release and are neuroprotective in experimental models of ischemic injury. | 2009 May |
|
Carbonic anhydrase inhibitors. Cloning, characterization, and inhibition studies of a new beta-carbonic anhydrase from Mycobacterium tuberculosis. | 2009 May 14 |
|
Evaluation of the therapeutic potential of carbonic anhydrase inhibitors in two animal models of dystrophin deficient muscular dystrophy. | 2009 Nov 1 |
|
Methazolamide does not impair respiratory work performance in anesthetized rabbits. | 2009 Sep |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/methazolamide.html
Usual Adult Dose for Glaucoma
50 to 100 mg orally 2 or 3 times a day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14764447
Methazolamide (0.1 mM) inhibited acid-induced [CO(2)](t) increase in mice.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 16 16:31:50 UTC 2022
by
admin
on
Fri Dec 16 16:31:50 UTC 2022
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Record UNII |
W733B0S9SD
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Record Status |
Validated (UNII)
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LIVERTOX |
NBK548664
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NCI_THESAURUS |
C29577
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WHO-VATC |
QS01EC05
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S01EC05
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NCI_THESAURUS |
C448
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DTXSID1023281
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D008704
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SUB08843MIG
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1406005
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1741
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METHAZOLAMIDE
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6828
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2101958-72-7
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209-066-7
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M7304
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CHEMBL19
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882
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758426
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3269
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DB00703
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6826
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Methazolamide
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554-57-4
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C61318
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TRANSPORTER -> INHIBITOR | |||
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BINDING
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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