Methazolamide

Identification

Summary

Methazolamide is a carbonic anhydrase inhibitor used to treat open angle glaucoma and acute angle closure glaucoma.

Generic Name
Methazolamide
DrugBank Accession Number
DB00703
Background

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

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 236.26
Monoisotopic: 236.003782482
Chemical Formula
C5H8N4O3S2
Synonyms
  • Metazolamida
  • Methazolamid
  • Méthazolamide
  • Methazolamide
  • Methazolamidum
  • Methenamide
  • Neptazaneat
External IDs
  • L 584601
  • L-584601
  • VVP-808
  • VVP808

Pharmacology

Indication

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

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in treatment ofAcute angle-closure glaucoma••••••••••••
Management ofOpen-angle glaucoma••••••••••••
Contraindications & Blackbox Warnings
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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
Humans
ACarbonic anhydrase 4
inhibitor
Humans
ACarbonic anhydrase 2
inhibitor
Humans
ACarbonic anhydrase 7
inhibitor
Humans
UCarbonic anhydrase 3
inhibitor
Humans
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

Adverse Effects
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Toxicity

Electrolyte imbalance, development of an acidotic state, and central nervous system effects might be expected to occur in the case of an overdose.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirMethazolamide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AbaloparatideThe risk or severity of adverse effects can be increased when Methazolamide is combined with Abaloparatide.
AcarboseThe therapeutic efficacy of Acarbose can be increased when used in combination with Methazolamide.
AcebutololThe risk or severity of adverse effects can be increased when Methazolamide is combined with Acebutolol.
AceclofenacMethazolamide may increase the excretion rate of Aceclofenac which could result in a lower serum level and potentially a reduction in efficacy.
Food Interactions
  • Drink plenty of fluids.
  • Take with food.

Products

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International/Other Brands
Naptazane (Fera Pharmaceuticals)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MethazolamideTablet50 mgOralAa Pharma Inc2002-07-25Not applicableCanada flag
Neptazane Tablets 25mgTablet25 mgOralWyeth Ayerst Canada Inc.1998-07-242000-08-02Canada flag
Neptazane Tablets 25mg USPTablet25 mgOralStorz, Division Of Wyeth Ayerst Canada Inc.1995-12-311999-08-12Canada flag
Neptazane Tablets 50mgTablet50 mgOralWyeth Ayerst Canada Inc.1998-12-232002-05-17Canada flag
Neptazane Tablets 50mgTablet50 mgOralStorz, Division Of Wyeth Ayerst Canada Inc.1993-12-311999-08-12Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MethazolamideTablet25 mg/1Oralbryant ranch prepack2014-11-06Not applicableUS flag
MethazolamideTablet25 mg/1OralSandoz Inc1993-06-302021-09-30US flag
MethazolamideTablet50 mg/1OralCarilion Materials Management2010-06-22Not applicableUS flag
MethazolamideTablet25 mg/1OralPrecision Dose, Inc.2023-11-30Not applicableUS flag
MethazolamideTablet25 mg/1OralGolden State Medical Supply, Inc.1993-06-30Not applicableUS flag

Categories

ATC Codes
G01AE10 — Combinations of sulfonamidesS01EC05 — Methazolamide
Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
W733B0S9SD
CAS number
554-57-4
InChI Key
FLOSMHQXBMRNHR-QPJJXVBHSA-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+
IUPAC Name
N-[(2E)-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

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. [Article]
  2. Shirato S, Kagaya F, Suzuki Y, Joukou S: Stevens-Johnson syndrome induced by methazolamide treatment. Arch Ophthalmol. 1997 Apr;115(4):550-3. [Article]
  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. [Article]
KEGG Drug
D00655
KEGG Compound
C07764
PubChem Compound
4100
PubChem Substance
46506393
ChemSpider
10438315
BindingDB
50013792
RxNav
6826
ChEBI
6822
ChEMBL
CHEMBL19
ZINC
ZINC000100019188
Therapeutic Targets Database
DAP000599
PharmGKB
PA450413
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Methazolamide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentOpen Angle Glaucoma (OAG)1
4CompletedBasic ScienceAltitude Sickness / Pulmonary Hypertension (PH)1
4CompletedBasic ScienceHypoxia1
4CompletedPreventionMountain Sickness1
4RecruitingBasic ScienceHigh Altitude Effects1

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)-6.1Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area105.19 Å2Chemaxon
Rotatable Bond Count1Chemaxon
Refractivity51.3 m3·mol-1Chemaxon
Polarizability21.11 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/MSsplash10-000i-0090000000-2c05c8c96a50b4ad000d
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9020000000-49a21962f41e2bed8240
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9020000000-1e9b3db331e1d7305008
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-002b-3920000000-0829f221d6b0e59a8dd7
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9000000000-e75b3b179b0854f5e66d
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-9400000000-1c2274b11dd22326adda
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Details
1. Carbonic anhydrase 1
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Lindskog S: Structure and mechanism of carbonic anhydrase. Pharmacol Ther. 1997;74(1):1-20. [Article]
Details
2. Carbonic anhydrase 4
Kind
Protein
Organism
Humans
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. [Article]
Details
3. Carbonic anhydrase 2
Kind
Protein
Organism
Humans
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. [Article]
Details
4. Carbonic anhydrase 7
Kind
Protein
Organism
Humans
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. [Article]
Details
5. Carbonic anhydrase 3
Kind
Protein
Organism
Humans
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. [Article]

Transporters

Kind
Protein
Organism
Humans
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48