Identification
- Generic Name
- Ethoxzolamide
- DrugBank Accession Number
- DB00311
- Background
Ethoxzolamide is a sulfonamide used as diuretic and in glaucoma. It inhibits carbonic anhydrase activity in proximal renal tubules to decrease reabsorption of water, sodium, potassium, bicarbonate. Its pharmacological activity thus confers the risk for hypokalemia.
- Type
- Small Molecule
- Groups
- Withdrawn
- Structure
Structure for Ethoxzolamide (DB00311)
- Weight
- Average: 258.317
Monoisotopic: 258.013283576 - Chemical Formula
- C9H10N2O3S2
- Synonyms
- 6-Ethoxy-1,3-benzothiazole-2-sulfonamide
- Ethoxazolamide
- Ethoxyzolamide
Pharmacology
- Indication
For use in the treatment of duodenal ulcers, as a diuretic, and in the treatment of glaucoma, and may also be useful in the treatment of seizures associated with epilepsy.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Ethoxzolamide is an inhibitor of the carbonic anhydrase enzyme in proximal renal tubules that works by decreasing the reabsorption of water, sodium, potassium, bicarbonate. It also decreases the activity of carbonic anhydrase expressed in the CNS, which leads to increased seizure threshold. Inhibition of carbonic anhydrase in the eye contributes to its effect of reducing intraocular pressure and decreasing aqueous humor.
- Mechanism of action
Ethoxzolamide binds to and inhibits carbonic anhydrase I, which plays an essential role in facilitating the transport of CO2 and H+ in the intracellular space, across biological membranes, and in the layers of the extracellular space. Through inhibition of the enzyme, the balance of applicable membrane equilibrium systems are affected.
Target Actions Organism ACarbonic anhydrase 2 inhibitorHumans ACarbonic anhydrase 4 inhibitorHumans ACarbonic anhydrase 7 inhibitorHumans ACarbonic anhydrase 1 inhibitorHumans UCarbonic anhydrase 3 inhibitorHumans - Absorption
Rapidly absorbed with 65% bioavailability
- Volume of distribution
Not Available
- Protein binding
~89%
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
2.5-5.5 hours
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Ethoxzolamide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy. Acarbose The therapeutic efficacy of Acarbose can be increased when used in combination with Ethoxzolamide. Aceclofenac Ethoxzolamide may increase the excretion rate of Aceclofenac which could result in a lower serum level and potentially a reduction in efficacy. Acemetacin The therapeutic efficacy of Ethoxzolamide can be decreased when used in combination with Acemetacin. Acetaminophen Ethoxzolamide may increase the excretion rate of Acetaminophen which could result in a lower serum level and potentially a reduction in efficacy. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Cardrase (PHARMACIA AND UPJOHN) / Ethamide (ALLERGAN)
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzothiazoles. These are organic compounds containing a benzene fused to a thiazole ring (a five-membered ring with four carbon atoms, one nitrogen atom and one sulfur atom).
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzothiazoles
- Sub Class
- Not Available
- Direct Parent
- Benzothiazoles
- Alternative Parents
- Alkyl aryl ethers / Organosulfonamides / Benzenoids / Thiazoles / Heteroaromatic compounds / Aminosulfonyl compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides show 1 more
- Substituents
- 1,3-benzothiazole / Alkyl aryl ether / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Ether / Heteroaromatic compound / Hydrocarbon derivative show 12 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- benzothiazoles, sulfonamide (CHEBI:101096)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Z52H4811WX
- CAS number
- 452-35-7
- InChI Key
- OUZWUKMCLIBBOG-UHFFFAOYSA-N
- InChI
- InChI=1S/C9H10N2O3S2/c1-2-14-6-3-4-7-8(5-6)15-9(11-7)16(10,12)13/h3-5H,2H2,1H3,(H2,10,12,13)
- IUPAC Name
- 6-ethoxy-1,3-benzothiazole-2-sulfonamide
- SMILES
- CCOC1=CC2=C(C=C1)N=C(S2)S(N)(=O)=O
References
- Synthesis Reference
Korman, J.; U.S. Patent 2,868,800; January 13, 1959; assigned to The Upjohn Company.
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014456
- KEGG Drug
- D02441
- PubChem Compound
- 3295
- PubChem Substance
- 46509023
- ChemSpider
- 3179
- BindingDB
- 10882
- ChEBI
- 101096
- ChEMBL
- CHEMBL18
- ZINC
- ZINC000000056721
- Therapeutic Targets Database
- DAP000598
- PharmGKB
- PA164754743
- PDBe Ligand
- EZL
- Wikipedia
- Ethoxzolamide
- PDB Entries
- 3caj / 3dcw / 3dd0 / 3mdz / 5jn9 / 5tt3 / 6bcc / 6mwi / 6ql2
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Pharmacia and upjohn co
- Allergan pharmaceutical
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 188-190.5 Korman, J.; U.S. Patent 2,868,800; January 13, 1959; assigned to The Upjohn Company. water solubility 40 mg/L YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 2.01 HANSCH,C ET AL. (1995) logS -3.81 ADME Research, USCD - Predicted Properties
Property Value Source Water Solubility 0.688 mg/mL ALOGPS logP 1.87 ALOGPS logP 1.6 Chemaxon logS -2.6 ALOGPS pKa (Strongest Acidic) 7.51 Chemaxon pKa (Strongest Basic) -1.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 82.28 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 59.97 m3·mol-1 Chemaxon Polarizability 25.27 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.8667 Caco-2 permeable - 0.6038 P-glycoprotein substrate Non-substrate 0.6875 P-glycoprotein inhibitor I Non-inhibitor 0.8793 P-glycoprotein inhibitor II Non-inhibitor 0.9528 Renal organic cation transporter Non-inhibitor 0.8576 CYP450 2C9 substrate Non-substrate 0.8346 CYP450 2D6 substrate Non-substrate 0.7982 CYP450 3A4 substrate Non-substrate 0.6017 CYP450 1A2 substrate Inhibitor 0.6223 CYP450 2C9 inhibitor Inhibitor 0.62 CYP450 2D6 inhibitor Non-inhibitor 0.8842 CYP450 2C19 inhibitor Inhibitor 0.6582 CYP450 3A4 inhibitor Non-inhibitor 0.6471 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5599 Ames test Non AMES toxic 0.5832 Carcinogenicity Non-carcinogens 0.7065 Biodegradation Not ready biodegradable 0.9846 Rat acute toxicity 2.5056 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9429 hERG inhibition (predictor II) Non-inhibitor 0.8419
Spectra
- Mass Spec (NIST)
- Download (10.1 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 162.4085459 predictedDarkChem Lite v0.1.0 [M-H]- 162.8913459 predictedDarkChem Lite v0.1.0 [M-H]- 151.90479 predictedDeepCCS 1.0 (2019) [M+H]+ 162.8070459 predictedDarkChem Lite v0.1.0 [M+H]+ 163.2533459 predictedDarkChem Lite v0.1.0 [M+H]+ 154.2628 predictedDeepCCS 1.0 (2019) [M+Na]+ 162.9455459 predictedDarkChem Lite v0.1.0 [M+Na]+ 163.0169459 predictedDarkChem Lite v0.1.0 [M+Na]+ 160.35606 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- 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
- 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]
- 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
- 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]
- 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
- 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]
- 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
- Kohling R, Vreugdenhil M, Bracci E, Jefferys JG: Ictal epileptiform activity is facilitated by hippocampal GABAA receptor-mediated oscillations. J Neurosci. 2000 Sep 15;20(18):6820-9. [Article]
- Perez Velazquez JL: Bicarbonate-dependent depolarizing potentials in pyramidal cells and interneurons during epileptiform activity. Eur J Neurosci. 2003 Sep;18(5):1337-42. [Article]
- Heck RW, Tanhauser SM, Manda R, Tu C, Laipis PJ, Silverman DN: Catalytic properties of mouse carbonic anhydrase V. J Biol Chem. 1994 Oct 7;269(40):24742-6. [Article]
- Siffert W, Gros G: Carbonic anhydrase C in white-skeletal-muscle tissue. Biochem J. 1982 Sep 1;205(3):559-66. [Article]
- 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]
- Bertucci A, Innocenti A, Zoccola D, Scozzafava A, Tambutte S, Supuran CT: Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorg Med Chem. 2009 Jul 15;17(14):5054-8. doi: 10.1016/j.bmc.2009.05.063. Epub 2009 May 30. [Article]
- 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
- 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
- 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 November 03, 2023 23:40