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Identification
NameEthoxzolamide
Accession NumberDB00311  (APRD00732, DB07727)
TypeSmall Molecule
GroupsWithdrawn
Description

A carbonic anhydrase inhibitor used as diuretic and in glaucoma. It may cause hypokalemia. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
6-Ethoxy-1,3-benzothiazole-2-sulfonamideNot AvailableIUPAC
EthoxazolamideNot AvailableNot Available
EthoxyzolamideNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
CardrasePHARMACIA AND UPJOHN
EthamideALLERGAN
Brand mixturesNot Available
Categories
CAS number452-35-7
WeightAverage: 258.317
Monoisotopic: 258.013283576
Chemical FormulaC9H10N2O3S2
InChI KeyOUZWUKMCLIBBOG-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
Mass Specshow(10.1 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzothiazoles
SubclassNot Available
Direct parentBenzothiazoles
Alternative parentsPhenol Ethers; Alkyl Aryl Ethers; Sulfonamides; Thiazoles; Sulfonyls; Polyamines
Substituentsphenol ether; alkyl aryl ether; benzene; sulfonyl; thiazole; azole; sulfonic acid derivative; sulfonamide; polyamine; ether; organonitrogen compound
Classification descriptionThis compound belongs to the benzothiazoles. These are organic compounds containing a benzene fused to a thiazole ring (a five-member ring with four carbon atoms, one nitrogen atom and one sulfur atom).
Pharmacology
IndicationFor 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.
PharmacodynamicsEthoxzolamide, a sulfonamide, inhibits carbonic anhydrase activity in proximal renal tubules to decrease reabsorption of water, sodium, potassium, bicarbonate. It also decreases carbonic anhydrase in the CNS, increasing the seizure threshold. This reduction in carbonic anhydrase also reduces the intraocular pressure in the eye by decreasing aqueous humor.
Mechanism of actionEthoxzolamide binds and inhibits carbonic anhydrase I. Carbonic anhydrase plays an essential role in facilitating the transport of carbon dioxide and protons in the intracellular space, across biological membranes and in the layers of the extracellular space. The inhibition of this enzyme effects the balance of applicable membrane equilibrium systems. This reduction in carbonic anhydrase also reduces the intraocular pressure in the eye by decreasing aqueous humor.
AbsorptionRapidly absorbed with 65% bioavailability
Volume of distributionNot Available
Protein binding~89%
Metabolism
Route of eliminationNot Available
Half life2.5-5.5 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrate Inhibitor 0.62
CYP450 2D6 substrate Non-inhibitor 0.8842
CYP450 2C19 substrate Inhibitor 0.6582
CYP450 3A4 substrate 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
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
  • Allergan pharmaceutical
PackagersNot Available
Dosage forms
FormRouteStrength
CapsuleOral
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point188-190.5Korman, J.; U.S. Patent 2,868,800; January 13, 1959; assigned to The Upjohn Company.
water solubility40 mg/LYALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.01HANSCH,C ET AL. (1995)
logS-3.81ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.688ALOGPS
logP1.87ALOGPS
logP1.6ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)7.51ChemAxon
pKa (Strongest Basic)-1.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area82.28 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity59.97 m3·mol-1ChemAxon
Polarizability25.27 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Korman, J.; U.S. Patent 2,868,800; January 13, 1959; assigned to The Upjohn Company.

General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD02441
PubChem Compound3295
PubChem Substance46509023
ChemSpider3179
BindingDB10882
ChEBI101096
ChEMBLCHEMBL18
Therapeutic Targets DatabaseDAP000598
PharmGKBPA164754743
HETEZL
WikipediaEthoxzolamide
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Carbonic anhydrase 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 1 P00915 Details

References:

  1. 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. Pubmed
  2. Perez Velazquez JL: Bicarbonate-dependent depolarizing potentials in pyramidal cells and interneurons during epileptiform activity. Eur J Neurosci. 2003 Sep;18(5):1337-42. Pubmed
  3. 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. Pubmed
  4. Siffert W, Gros G: Carbonic anhydrase C in white-skeletal-muscle tissue. Biochem J. 1982 Sep 1;205(3):559-66. Pubmed
  5. 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
  6. 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. Epub 2009 May 30. Pubmed

2. Carbonic anhydrase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 2 P00918 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 4 P22748 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 7 P43166 Details

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

Transporters

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

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

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Drug created on June 13, 2005 07:24 / Updated on April 22, 2014 10:43