You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameMethazolamide
Accession NumberDB00703  (APRD00740)
TypeSmall Molecule
GroupsApproved
Description

A carbonic anhydrase inhibitor that is used as a diuretic and in the treatment of glaucoma. [PubChem]

Structure
Thumb
Synonyms
Metazolamida
Methazolamid
Méthazolamide
Methazolamidum
Methenamide
Neptazane
Neptazaneat
External Identifiers
  • L 584601
  • L-584601
  • VVP-808
  • VVP808
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Methazolamidetablet50 mgoralAa Pharma Inc2002-07-25Not applicableCanada
Neptazane Tablets 25mgtablet25 mgoralWyeth Ayerst Canada Inc.1998-07-242000-08-02Canada
Neptazane Tablets 25mg USPtablet25 mgoralStorz, Division Of Wyeth Ayerst Canada Inc.1995-12-311999-08-12Canada
Neptazane Tablets 50mgtablet50 mgoralWyeth Ayerst Canada Inc.1998-12-232002-05-17Canada
Neptazane Tablets 50mgtablet50 mgoralStorz, Division Of Wyeth Ayerst Canada Inc.1993-12-311999-08-12Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Methazolamidetablet25 mg/1oralANI Pharmaceuticals, Inc.2014-11-06Not applicableUs
Methazolamidetablet50 mg/1oralCarilion Materials Management2010-06-22Not applicableUs
Methazolamidetablet25 mg/1oralEffcon Laboratories, Inc.1994-07-14Not applicableUs
Methazolamidetablet25 mg/1oralSandoz Inc1993-06-30Not applicableUs
Methazolamidetablet50 mg/1oralEffcon Laboratories, Inc.1994-07-18Not applicableUs
Methazolamidetablet50 mg/1oralSandoz Inc1993-06-30Not applicableUs
Methazolamidetablet50 mg/1oralPhysicians Total Care, Inc.2006-12-12Not applicableUs
Methazolamidetablet50 mg/1oralPaddock Laboratories, LLC2014-09-30Not applicableUs
Methazolamidetablet50 mg/1oralFera Pharmaceuticals2010-06-22Not applicableUs
Methazolamidetablet25 mg/1oralPaddock Laboratories, LLC2014-09-30Not applicableUs
Methazolamidetablet25 mg/1oralFera Pharmaceuticals2010-06-22Not applicableUs
Methazolamidetablet50 mg/1oralANI Pharmaceuticals, Inc.2014-11-06Not applicableUs
Neptazanetablet25 mg/1oralPaddock Laboratories, LLC2015-01-12Not applicableUs
Neptazanetablet25 mg/1oralFera Pharmaceuticals2010-06-22Not applicableUs
Neptazanetablet50 mg/1oralPaddock Laboratories, LLC2015-01-12Not applicableUs
Neptazanetablet50 mg/1oralFera Pharmaceuticals2010-06-22Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
NaptazaneFera Pharmaceuticals
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIW733B0S9SD
CAS number554-57-4
WeightAverage: 236.26
Monoisotopic: 236.003782482
Chemical FormulaC5H8N4O3S2
InChI KeyFLOSMHQXBMRNHR-UHFFFAOYSA-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)
IUPAC Name
N-(3-methyl-5-sulfamoyl-2,3-dihydro-1,3,4-thiadiazol-2-ylidene)acetamide
SMILES
CN1N=C(SC1=NC(C)=O)S(N)(=O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as thiadiazole sulfonamides. These are heterocyclic compounds containing a thiazole ring substituted by at least one sulfonamide group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassThiadiazoles
Direct ParentThiadiazole sulfonamides
Alternative Parents
Substituents
  • 1,3,4-thiadiazole-2-sulfonamide
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • N-acylimine
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Organic oxide
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor treatment of chronic open-angle glaucoma and acute angle-closure glaucoma
PharmacodynamicsMethazolamide 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 actionMethazolamide 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.
Related Articles
AbsorptionMethazolamide is well absorbed from the gastrointestinal tract.
Volume of distribution
  • 17 to 23 L
Protein binding55%
MetabolismNot Available
Route of eliminationNot Available
Half life14 hours
ClearanceNot Available
ToxicityElectrolyte 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7104
Blood Brain Barrier+0.8117
Caco-2 permeable-0.6196
P-glycoprotein substrateNon-substrate0.8509
P-glycoprotein inhibitor INon-inhibitor0.9245
P-glycoprotein inhibitor IINon-inhibitor0.8896
Renal organic cation transporterNon-inhibitor0.8909
CYP450 2C9 substrateNon-substrate0.6189
CYP450 2D6 substrateNon-substrate0.8512
CYP450 3A4 substrateNon-substrate0.6898
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.6861
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8681
Ames testNon AMES toxic0.7032
CarcinogenicityNon-carcinogens0.7679
BiodegradationNot ready biodegradable0.9138
Rat acute toxicity2.2388 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9942
hERG inhibition (predictor II)Non-inhibitor0.9021
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Applied analytical industries
  • Mikart inc
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Lederle laboratories div american cyanamid co
Packagers
Dosage forms
FormRouteStrength
Tabletoral50 mg
Tabletoral25 mg/1
Tabletoral50 mg/1
Tabletoral25 mg
Prices
Unit descriptionCostUnit
Methazolamide powder27.0USD g
Methazolamide 50 mg tablet0.77USD tablet
Neptazane 25 mg tablet0.6USD tablet
Apo-Methazolamide 50 mg Tablet0.5USD tablet
Methazolamide 25 mg tablet0.49USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point213.5 °CPhysProp
water solubility3500 mg/LYALKOWSKY,SH & DANNENFELSER,RM (1992)
logP0.13HANSCH,C ET AL. (1995)
logS-1.83ADME Research, USCD
pKa7.30Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.74 mg/mLALOGPS
logP-0.2ALOGPS
logP-0.59ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)7.21ChemAxon
pKa (Strongest Basic)-3.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area105.19 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity51.3 m3·mol-1ChemAxon
Polarizability20.99 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General References
  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:10533697 ]
  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:9109770 ]
  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:12602587 ]
External Links
ATC CodesS01EC05
AHFS Codes
  • 52:10.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Methazolamide.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Methazolamide.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Methazolamide.
AmphetamineMethazolamide may decrease the excretion rate of Amphetamine which could result in a lower serum level and potentially a reduction in efficacy.
ButabarbitalButabarbital may increase the hypotensive activities of Methazolamide.
ButethalButethal may increase the hypotensive activities of Methazolamide.
CarbamazepineThe serum concentration of Carbamazepine can be increased when it is combined with Methazolamide.
CathinoneMethazolamide may decrease the excretion rate of Cathinone which could result in a lower serum level and potentially a reduction in efficacy.
DiclofenamideThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Methazolamide.
DuloxetineMethazolamide may increase the orthostatic hypotensive activities of Duloxetine.
EthoxzolamideThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Methazolamide.
FlecainideThe serum concentration of Flecainide can be increased when it is combined with Methazolamide.
HeptabarbitalHeptabarbital may increase the hypotensive activities of Methazolamide.
HexamethylenetetramineThe therapeutic efficacy of Hexamethylenetetramine can be decreased when used in combination with Methazolamide.
HexobarbitalHexobarbital may increase the hypotensive activities of Methazolamide.
LevodopaMethazolamide may increase the orthostatic hypotensive activities of Levodopa.
LithiumThe serum concentration of Lithium can be decreased when it is combined with Methazolamide.
MemantineMethazolamide may decrease the excretion rate of Memantine which could result in a lower serum level and potentially a reduction in efficacy.
MetforminThe risk or severity of adverse effects can be increased when Methazolamide is combined with Metformin.
MethohexitalMethohexital may increase the hypotensive activities of Methazolamide.
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Methazolamide.
NicorandilNicorandil may increase the hypotensive activities of Methazolamide.
PentobarbitalPentobarbital may increase the hypotensive activities of Methazolamide.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Methazolamide.
PhenytoinThe risk or severity of adverse effects can be increased when Methazolamide is combined with Phenytoin.
PrimidoneThe risk or severity of adverse effects can be increased when Methazolamide is combined with Primidone.
QuinidineMethazolamide may decrease the excretion rate of Quinidine which could result in a lower serum level and potentially a reduction in efficacy.
RisperidoneMethazolamide may increase the hypotensive activities of Risperidone.
SecobarbitalSecobarbital may increase the hypotensive activities of Methazolamide.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Methazolamide.
TriethylenetetramineThe serum concentration of Triethylenetetramine can be decreased when it is combined with Methazolamide.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Methazolamide.
Food Interactions
  • Take with food, more than 6 hours before bedtime increase liquid intake.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular Weight:
28870.0 Da
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:15110853 ]
  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:14684332 ]
  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:10533697 ]
  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:10649985 ]
  5. Lindskog S: Structure and mechanism of carbonic anhydrase. Pharmacol Ther. 1997;74(1):1-20. [PubMed:9336012 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate ex...
Gene Name:
CA2
Uniprot ID:
P00918
Molecular Weight:
29245.895 Da
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:18336310 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
Gene Name:
CA4
Uniprot ID:
P22748
Molecular Weight:
35032.075 Da
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:18336310 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA7
Uniprot ID:
P43166
Molecular Weight:
29658.235 Da
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:18336310 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
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.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
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, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
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.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
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.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
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 xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
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:10991988 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23