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
Synonyms
  • Metazolamida
  • Methazolamid
  • Méthazolamide
  • Methazolamidum
  • Methenamide
  • Neptazaneat
External IDs
L 584601 / L-584601 / VVP-808 / VVP808
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
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MethazolamideTablet25 mg/1OralTeva1994-01-012013-03-31Us
MethazolamideTablet50 mg/1OralEffcon Laboratories, Inc.1994-07-18Not applicableUs
MethazolamideTablet50 mg/1OralANI Pharmaceuticals, Inc.2014-11-06Not applicableUs
MethazolamideTablet25 mg/1OralSandoz1993-06-30Not applicableUs
MethazolamideTablet25 mg/1OralFera Pharmaceuticals2010-06-222013-06-14Us
MethazolamideTablet50 mg/1OralGolden State Medical Supply Inc.1993-06-30Not applicableUs
MethazolamideTablet50 mg/1OralCarilion Materials Management2010-06-22Not applicableUs
MethazolamideTablet50 mg/1OralPhysicians Total Care, Inc.2006-12-12Not applicableUs
MethazolamideTablet25 mg/1OralEffcon Laboratories, Inc.1994-07-14Not applicableUs
MethazolamideTablet50 mg/1OralPaddock Laboratories, LLC2014-09-30Not applicableUs
International/Other Brands
Naptazane (Fera Pharmaceuticals) / Neptazane
Categories
UNII
W733B0S9SD
CAS number
554-57-4
Weight
Average: 236.26
Monoisotopic: 236.003782482
Chemical Formula
C5H8N4O3S2
InChI Key
FLOSMHQXBMRNHR-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

Pharmacology

Indication

For treatment of chronic open-angle glaucoma and acute angle-closure glaucoma

Associated Conditions
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.

TargetActionsOrganism
ACarbonic anhydrase 1
inhibitor
Human
ACarbonic anhydrase 2
inhibitor
Human
ACarbonic anhydrase 4
inhibitor
Human
ACarbonic anhydrase 7
inhibitor
Human
UCarbonic anhydrase 3
inhibitor
Human
Absorption

Methazolamide is well absorbed from the gastrointestinal tract.

Volume of distribution
  • 17 to 23 L
Protein binding

55%

Metabolism
Not Available
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Methazolamide.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Methazolamide.
2,5-Dimethoxy-4-ethylamphetamineMethazolamide may decrease the excretion rate of 2,5-Dimethoxy-4-ethylamphetamine which could result in a higher serum level.
2,5-Dimethoxy-4-ethylthioamphetamineMethazolamide may decrease the excretion rate of 2,5-Dimethoxy-4-ethylthioamphetamine which could result in a higher serum level.
3,4-MethylenedioxyamphetamineMethazolamide may decrease the excretion rate of 3,4-Methylenedioxyamphetamine which could result in a higher serum level.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Methazolamide.
4-Bromo-2,5-dimethoxyamphetamineMethazolamide may decrease the excretion rate of 4-Bromo-2,5-dimethoxyamphetamine which could result in a higher serum level.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Methazolamide.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Methazolamide.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Methazolamide.
Food Interactions
  • Take with food, more than 6 hours before bedtime increase liquid intake.

References

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
KEGG Drug
D00655
KEGG Compound
C07764
PubChem Compound
4100
PubChem Substance
46506393
ChemSpider
21122102
BindingDB
10881
ChEBI
94513
ChEMBL
CHEMBL1335656
Therapeutic Targets Database
DAP000599
PharmGKB
PA450413
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Methazolamide
ATC Codes
S01EC05 — Methazolamide
AHFS Codes
  • 52:40.12 — Carbonic Anhydrase Inhibitors

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceMountain Sickness1
1, 2CompletedPreventionPhysiological Function in Low Oxygen Environment1
2WithdrawnTreatmentCervical Cancers1
3RecruitingPreventionGlaucoma1
4Active Not RecruitingPreventionMountain Sickness1
4CompletedBasic ScienceAltitude Sickness / Pulmonary Hypertension (PH)1
4CompletedBasic ScienceArterial hypoxia1
4CompletedPreventionGeneralized Aggressive Periodontitis1

Pharmacoeconomics

Manufacturers
  • Applied analytical industries
  • Mikart inc
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Lederle laboratories div american cyanamid co
Packagers
  • Akorn Inc.
  • Effcon Laboratories Inc.
  • Fera Pharmaceuticals
  • Heartland Repack Services LLC
  • Mikart Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Physicians Total Care Inc.
  • Prescript Pharmaceuticals
  • Professional Co.
  • Qualitest
  • Sandoz
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
TabletOral25 mg/1
TabletOral50 mg
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)213.5 °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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0910000000-054f4dbf60ebb492a9e8
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-1900000000-c3b2b928b831554ae1a0

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Thiadiazoles
Direct Parent
Thiadiazole sulfonamides
Alternative Parents
Organosulfonamides / Heteroaromatic compounds / Aminosulfonyl compounds / N-acylimines / Carboxylic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
1,3,4-thiadiazole-2-sulfonamide / Organosulfonic acid amide / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Sulfonyl / Heteroaromatic compound / Aminosulfonyl compound / N-acylimine / Carboxylic acid derivative / Azacycle
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Details
1. Carbonic anhydrase 1
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
Uniprot Name
Carbonic anhydrase 1
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]
Details
2. Carbonic anhydrase 2
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 in...
Gene Name
CA2
Uniprot ID
P00918
Uniprot Name
Carbonic anhydrase 2
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]
Details
3. Carbonic anhydrase 4
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 an...
Gene Name
CA4
Uniprot ID
P22748
Uniprot Name
Carbonic anhydrase 4
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]
Details
4. Carbonic anhydrase 7
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
Uniprot Name
Carbonic anhydrase 7
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]
Details
5. Carbonic anhydrase 3
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide.
Gene Name
CA3
Uniprot ID
P07451
Uniprot Name
Carbonic anhydrase 3
Molecular Weight
29557.215 Da
References
  1. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [PubMed:17826101]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
The data currently available for this enzyme inhibition is limited to one in vitro study.
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. van den Bongard HJ, Sparidans RW, Critchley DJ, Beijnen JH, Schellens JH: Pharmacokinetic drug-drug interaction of the novel anticancer agent E7070 and acenocoumarol. Invest New Drugs. 2004 Apr;22(2):151-8. [PubMed:14739663]
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
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]
  2. van den Bongard HJ, Sparidans RW, Critchley DJ, Beijnen JH, Schellens JH: Pharmacokinetic drug-drug interaction of the novel anticancer agent E7070 and acenocoumarol. Invest New Drugs. 2004 Apr;22(2):151-8. [PubMed:14739663]
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 ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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]
  2. van den Bongard HJ, Sparidans RW, Critchley DJ, Beijnen JH, Schellens JH: Pharmacokinetic drug-drug interaction of the novel anticancer agent E7070 and acenocoumarol. Invest New Drugs. 2004 Apr;22(2):151-8. [PubMed:14739663]

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 ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
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]

Drug created on June 13, 2005 07:24 / Updated on November 20, 2018 00:45