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Identification
Name Methazolamide
Accession Number DB00703 (APRD00740)
Type small molecule
Groups approved
Description

A carbonic anhydrase inhibitor that is used as a diuretic and in the treatment of glaucoma. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Methenamide
  • MZM
  • Naptazane
  • Neptazane
  • Neptazaneat
Brand name mixtures Not Available
Categories
  • Diuretics
  • Carbonic Anhydrase Inhibitors
CAS number 554-57-4
Weight Average: 236.272
Monoisotopic: 236.003781522
Chemical Formula C5H8N4O3S2
InChI Key InChIKey=FLOSMHQXBMRNHR-DAXSKMNVSA-N
InChI
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-
Plain Text
IUPAC Name
N-(3-methyl-5-sulfamoyl-2,3-dihydro-1,3,4-thiadiazol-2-ylidene)acetamide
SMILES
CN1N=C(S\C1=N/C(C)=O)S(N)(=O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Amino Ketones
  • Thiadiazoles
  • Sulfonyls
  • Sulfonamides
Substructures
  • Amino Ketones
  • Thiadiazoles
  • Sulfonyls
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Sulfonamides
  • Cyanamides
Pharmacology
Indication For treatment of chronic open-angle glaucoma and acute angle-closure glaucoma
Pharmacodynamics 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.
Mechanism of action 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.
Absorption Methazolamide is well absorbed from the gastrointestinal tract.
Volume of distribution
  • 17 to 23 L
Protein binding 55%
Metabolism
Route of elimination Not Available
Half life 14 hours
Clearance Not Available
Toxicity Electrolyte imbalance, development of an acidotic state, and central nervous system effects might be expected to occur in the case of an overdose.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Applied analytical industries
  • Mikart inc
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Lederle laboratories div american cyanamid co
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Methazolamide powder 27.0 USD g
Methazolamide 50 mg tablet 0.77 USD tablet
Neptazane 25 mg tablet 0.6 USD tablet
Apo-Methazolamide 50 mg Tablet 0.5 USD tablet
Methazolamide 25 mg tablet 0.49 USD tablet
Patents Not Available
Properties
State solid
Melting point 213.5 oC
Experimental Properties
Property Value Source
water solubility 3500 mg/L PhysProp
logP -1.6 PhysProp
logS -1.83 [ADME Research, USCD] PhysProp
pKa 7.30 Various sources
Predicted Properties
Property Value Source
water solubility 1.74e+00 g/l ALOGPS
logP -0.20 ALOGPS
logP -0.59 ChemAxon Molconvert
logS -2.13 ALOGPS
pKa 19.43 ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 105.19 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 51.30 ChemAxon Molconvert
polarizability 21.17 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Iyer GR, Bellantone RA, Taft DR: In vitro characterization of the erythrocyte distribution of methazolamide: a model of erythrocyte transport and binding kinetics. J Pharmacokinet Biopharm. 1999 Feb;27(1):45-66. Pubmed
  2. Shirato S, Kagaya F, Suzuki Y, Joukou S: Stevens-Johnson syndrome induced by methazolamide treatment. Arch Ophthalmol. 1997 Apr;115(4):550-3. Pubmed
  3. Skorobohach BJ, Ward DA, Hendrix DV: Effects of oral administration of methazolamide on intraocular pressure and aqueous humor flow rate in clinically normal dogs. Am J Vet Res. 2003 Feb;64(2):183-7. Pubmed
External Links
Resource Link
KEGG Drug D00655 Link_out
KEGG Compound C07764 Link_out
PubChem Compound 4100 Link_out
PubChem Substance 46506393 Link_out
ChemSpider 3958 Link_out
BindingDB 10881 Link_out
Therapeutic Targets Database DAP000599 Link_out
PharmGKB PA450413 Link_out
Drug Product Database 2245882 Link_out
RxList http://www.rxlist.com/cgi/generic2/methaz.htm Link_out
Drugs.com http://www.drugs.com/cdi/methazolamide.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Methazolamide Link_out
ATC Codes
  • S01EC05
AHFS Codes
  • 52:10.00
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take with food, more than 6 hours before bedtime increase liquid intake.
Targets

1. Carbonic anhydrase 1

Pharmacological action: yes
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P00915 Link_out
Gene: CA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ilies MA, Masereel B, Rolin S, Scozzafava A, Campeanu G, Cimpeanu V, Supuran CT: Carbonic anhydrase inhibitors: aromatic and heterocyclic sulfonamides incorporating adamantyl moieties with strong anticonvulsant activity. Bioorg Med Chem. 2004 May 15;12(10):2717-26. Pubmed
  2. Winum JY, Casini A, Mincione F, Starnotti M, Montero JL, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits. Bioorg Med Chem Lett. 2004 Jan 5;14(1):225-9. Pubmed
  3. Iyer GR, Bellantone RA, Taft DR: In vitro characterization of the erythrocyte distribution of methazolamide: a model of erythrocyte transport and binding kinetics. J Pharmacokinet Biopharm. 1999 Feb;27(1):45-66. Pubmed
  4. Scozzafava A, Briganti F, Ilies MA, Supuran CT: Carbonic anhydrase inhibitors: synthesis of membrane-impermeant low molecular weight sulfonamides possessing in vivo selectivity for the membrane-bound versus cytosolic isozymes. J Med Chem. 2000 Jan 27;43(2):292-300. Pubmed
  5. Lindskog S: Structure and mechanism of carbonic anhydrase. Pharmacol Ther. 1997;74(1):1-20. Pubmed

2. Carbonic anhydrase 2

Pharmacological action: yes
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P00918 Link_out
Gene: CA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mincione F, Scozzafava A, Supuran CT: The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr Pharm Des. 2008;14(7):649-54. Pubmed

3. Carbonic anhydrase 4

Pharmacological action: yes
Actions: inhibitor

Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4

Organism class: human
UniProt ID: P22748 Link_out
Gene: CA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mincione F, Scozzafava A, Supuran CT: The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr Pharm Des. 2008;14(7):649-54. Pubmed

4. Carbonic anhydrase 7

Pharmacological action: yes
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P43166 Link_out
Gene: CA7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mincione F, Scozzafava A, Supuran CT: The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr Pharm Des. 2008;14(7):649-54. Pubmed
Enzymes

1. Cytochrome P450 2C19

Actions: inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2E1

Actions: inhibitor

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 3A4

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Uwai Y, Saito H, Hashimoto Y, Inui KI: Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000 Oct;295(1):261-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:42

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.