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Identification
NameEthoxzolamide
Accession NumberDB00311  (APRD00732, DB07727)
TypeSmall Molecule
GroupsWithdrawn
DescriptionA carbonic anhydrase inhibitor used as diuretic and in glaucoma. It may cause hypokalemia. [PubChem]
Structure
Thumb
Synonyms
6-Ethoxy-1,3-benzothiazole-2-sulfonamide
Ethoxazolamide
Ethoxyzolamide
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CardrasePHARMACIA AND UPJOHN
EthamideALLERGAN
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIZ52H4811WX
CAS number452-35-7
WeightAverage: 258.317
Monoisotopic: 258.013283576
Chemical FormulaC9H10N2O3S2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazoles
Sub ClassNot Available
Direct ParentBenzothiazoles
Alternative Parents
Substituents
  • 1,3-benzothiazole
  • Alkyl aryl ether
  • Benzenoid
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Thiazole
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Azole
  • Azacycle
  • Ether
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
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.
Related Articles
AbsorptionRapidly absorbed with 65% bioavailability
Volume of distributionNot Available
Protein binding~89%
MetabolismNot Available
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
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8667
Caco-2 permeable-0.6038
P-glycoprotein substrateNon-substrate0.6875
P-glycoprotein inhibitor INon-inhibitor0.8793
P-glycoprotein inhibitor IINon-inhibitor0.9528
Renal organic cation transporterNon-inhibitor0.8576
CYP450 2C9 substrateNon-substrate0.8346
CYP450 2D6 substrateNon-substrate0.7982
CYP450 3A4 substrateNon-substrate0.6017
CYP450 1A2 substrateInhibitor0.6223
CYP450 2C9 inhibitorInhibitor0.62
CYP450 2D6 inhibitorNon-inhibitor0.8842
CYP450 2C19 inhibitorInhibitor0.6582
CYP450 3A4 inhibitorNon-inhibitor0.6471
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5599
Ames testNon AMES toxic0.5832
CarcinogenicityNon-carcinogens0.7065
BiodegradationNot ready biodegradable0.9846
Rat acute toxicity2.5056 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9429
hERG inhibition (predictor II)Non-inhibitor0.8419
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
  • Allergan pharmaceutical
PackagersNot Available
Dosage formsNot Available
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 Solubility0.688 mg/mLALOGPS
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (10.1 KB)
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 Reference

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

General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
3,4-MethylenedioxyamphetamineEthoxzolamide may decrease the excretion rate of 3,4-Methylenedioxyamphetamine which could result in a lower serum level and potentially a reduction in efficacy.
3,4-MethylenedioxymethamphetamineEthoxzolamide may decrease the excretion rate of 3,4-Methylenedioxymethamphetamine which could result in a lower serum level and potentially a reduction in efficacy.
AcetazolamideThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Acetazolamide.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Ethoxzolamide.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Ethoxzolamide.
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Ethoxzolamide.
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Aminosalicylic Acid is combined with Ethoxzolamide.
AmphetamineEthoxzolamide may decrease the excretion rate of Amphetamine which could result in a lower serum level and potentially a reduction in efficacy.
BenzphetamineEthoxzolamide may decrease the excretion rate of Benzphetamine which could result in a lower serum level and potentially a reduction in efficacy.
BezitramideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Ethoxzolamide.
BrinzolamideThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Brinzolamide.
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Ethoxzolamide.
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Ethoxzolamide.
CarbamazepineThe serum concentration of Carbamazepine can be increased when it is combined with Ethoxzolamide.
CarfentanilThe risk or severity of adverse effects can be increased when Carfentanil is combined with Ethoxzolamide.
ChlorphentermineEthoxzolamide may decrease the excretion rate of Chlorphentermine which could result in a lower serum level and potentially a reduction in efficacy.
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Ethoxzolamide.
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Ethoxzolamide.
DextroamphetamineEthoxzolamide may decrease the excretion rate of Dextroamphetamine which could result in a lower serum level and potentially a reduction in efficacy.
DextromoramideThe risk or severity of adverse effects can be increased when Dextromoramide is combined with Ethoxzolamide.
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Ethoxzolamide.
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Ethoxzolamide.
DiclofenamideThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Diclofenamide.
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Ethoxzolamide.
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Ethoxzolamide.
DihydroetorphineThe risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Ethoxzolamide.
DihydromorphineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Ethoxzolamide.
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Ethoxzolamide.
DorzolamideThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Dorzolamide.
DPDPEThe risk or severity of adverse effects can be increased when DPDPE is combined with Ethoxzolamide.
EthylmorphineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Ethoxzolamide.
EtorphineThe risk or severity of adverse effects can be increased when Etorphine is combined with Ethoxzolamide.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Ethoxzolamide.
FlecainideThe serum concentration of Flecainide can be increased when it is combined with Ethoxzolamide.
FosphenytoinThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Fosphenytoin.
HeroinThe risk or severity of adverse effects can be increased when Heroin is combined with Ethoxzolamide.
HexamethylenetetramineThe therapeutic efficacy of Hexamethylenetetramine can be decreased when used in combination with Ethoxzolamide.
HydrocodoneThe risk or severity of adverse effects can be increased when Hydrocodone is combined with Ethoxzolamide.
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Ethoxzolamide.
Hydroxyamphetamine hydrobromideEthoxzolamide may decrease the excretion rate of Hydroxyamphetamine hydrobromide which could result in a lower serum level and potentially a reduction in efficacy.
KetobemidoneThe risk or severity of adverse effects can be increased when Ketobemidone is combined with Ethoxzolamide.
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Ethoxzolamide.
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Ethoxzolamide.
LisdexamfetamineEthoxzolamide may decrease the excretion rate of Lisdexamfetamine which could result in a lower serum level and potentially a reduction in efficacy.
LithiumThe serum concentration of Lithium can be decreased when it is combined with Ethoxzolamide.
LofentanilThe risk or severity of adverse effects can be increased when Lofentanil is combined with Ethoxzolamide.
MecamylamineThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Mecamylamine.
MemantineEthoxzolamide may decrease the excretion rate of Memantine which could result in a lower serum level and potentially a reduction in efficacy.
MephentermineEthoxzolamide may decrease the excretion rate of Mephentermine which could result in a lower serum level and potentially a reduction in efficacy.
MesalazineThe risk or severity of adverse effects can be increased when Mesalazine is combined with Ethoxzolamide.
MetforminThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Metformin.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Ethoxzolamide.
Methadyl AcetateThe risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Ethoxzolamide.
MethamphetamineEthoxzolamide may decrease the excretion rate of Methamphetamine which could result in a lower serum level and potentially a reduction in efficacy.
MethazolamideThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Methazolamide.
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Ethoxzolamide.
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Ethoxzolamide.
NormethadoneThe risk or severity of adverse effects can be increased when Normethadone is combined with Ethoxzolamide.
OpiumThe risk or severity of adverse effects can be increased when Opium is combined with Ethoxzolamide.
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Ethoxzolamide.
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Ethoxzolamide.
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Ethoxzolamide.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Ethoxzolamide.
PhentermineEthoxzolamide may decrease the excretion rate of Phentermine which could result in a lower serum level and potentially a reduction in efficacy.
PhenytoinThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Phenytoin.
PrimidoneThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Primidone.
QuinidineEthoxzolamide may decrease the excretion rate of Quinidine which could result in a lower serum level and potentially a reduction in efficacy.
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Ethoxzolamide.
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Ethoxzolamide.
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Ethoxzolamide.
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Ethoxzolamide.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Ethoxzolamide.
Food InteractionsNot Available

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. 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:10995826 ]
  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:12956733 ]
  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:7929150 ]
  4. Siffert W, Gros G: Carbonic anhydrase C in white-skeletal-muscle tissue. Biochem J. 1982 Sep 1;205(3):559-66. [PubMed:6816217 ]
  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:10649985 ]
  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. doi: 10.1016/j.bmc.2009.05.063. Epub 2009 May 30. [PubMed:19520577 ]
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 ]

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 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23