ETHOXZOLAMIDE

First approved in 1957

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H10N2O3S2
Molecular Weight	258.317
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC1=CC=C2N=C(SC2=C1)S(N)(=O)=O

InChI

InChIKey=OUZWUKMCLIBBOG-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C9H10N2O3S2
Molecular Weight	258.317
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C65561
Curator's Comment: description was created based on several sources, including https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011047

Ethoxzolamide is a carbonic anhydrase I inhibitor. It is used in the treatment of glaucoma and duodenal ulcers, and as a diuretic. Ethoxzolamide was marketed under trade name Cadrase, but is now discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Carbonic anhydrase 6 Target ID: CHEMBL2095180 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17125255	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Duodenal ulcer 42 Sources: https://www.ncbi.nlm.nih.gov/mesh/68005016	Primary		Approved 8429	CARDRASE Approved Use Ethoxzolamide is a carbonic anhydrase inhibitor used as diuretic and in glaucoma.
Glaucoma 57 Sources: https://www.ncbi.nlm.nih.gov/mesh/68005016	Primary		Approved 8429	CARDRASE Approved Use Ethoxzolamide is a carbonic anhydrase inhibitor used as diuretic and in glaucoma.

T_1/2

Value	Dose	Co-administered	Analyte	Population
300 min REVIEW https://journals.physiology.org/doi/abs/10.1152/physrev.1967.47.4.595	, oral		ETHOXZOLAMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
11% OTHER https://go.drugbank.com/drugs/DB00311	unknown, unknown		ETHOXZOLAMIDE serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
4% REVIEW https://journals.physiology.org/doi/abs/10.1152/physrev.1967.47.4.595	, oral		ETHOXZOLAMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
250 mg 4 times / day multiple, oral Highest studied dose Dose: 250 mg, 4 times / day Route: oral Route: multiple Dose: 250 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499	unhealthy, 48 - 73 n = 13 Health Status: unhealthy Condition: Heart failure Age Group: 48 - 73 Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499	Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499
500 mg 1 times / day multiple, oral Recommended Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499	unhealthy, 48 - 73 n = 13 Health Status: unhealthy Condition: Heart failure Age Group: 48 - 73 Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499	Disc. AE: Diarrhea, Paresthesia... AEs leading to discontinuation/dose reduction: Diarrhea (15.4%) Paresthesia (7.7%) Fatigue (7.7%) Weakness (7.7%) Leg cramps (7.7%) Abdominal cramps (7.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499
125 mg 6 times / day multiple, oral Recommended Dose: 125 mg, 6 times / day Route: oral Route: multiple Dose: 125 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13817990 Page: p.149/433	unhealthy n = 18 Health Status: unhealthy Condition: Chronic simple glaucoma Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/13817990 Page: p.149/433	Disc. AE: Muscle cramps, Dizziness... AEs leading to discontinuation/dose reduction: Muscle cramps (severe, 5.5%) Dizziness (severe, 5.5%) Generalized eruption (severe, 5.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/13817990 Page: p.149/433

AEs

AE	Significance	Dose	Population
Diarrhea	15.4% Disc. AE	500 mg 1 times / day multiple, oral Recommended Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499	unhealthy, 48 - 73 n = 13 Health Status: unhealthy Condition: Heart failure Age Group: 48 - 73 Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499
Abdominal cramps	7.7% Disc. AE	500 mg 1 times / day multiple, oral Recommended Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499	unhealthy, 48 - 73 n = 13 Health Status: unhealthy Condition: Heart failure Age Group: 48 - 73 Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499
Fatigue	7.7% Disc. AE	500 mg 1 times / day multiple, oral Recommended Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499	unhealthy, 48 - 73 n = 13 Health Status: unhealthy Condition: Heart failure Age Group: 48 - 73 Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499
Leg cramps	7.7% Disc. AE	500 mg 1 times / day multiple, oral Recommended Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499	unhealthy, 48 - 73 n = 13 Health Status: unhealthy Condition: Heart failure Age Group: 48 - 73 Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499
Paresthesia	7.7% Disc. AE	500 mg 1 times / day multiple, oral Recommended Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499	unhealthy, 48 - 73 n = 13 Health Status: unhealthy Condition: Heart failure Age Group: 48 - 73 Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499
Weakness	7.7% Disc. AE	500 mg 1 times / day multiple, oral Recommended Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499	unhealthy, 48 - 73 n = 13 Health Status: unhealthy Condition: Heart failure Age Group: 48 - 73 Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/13520609 Page: p.499
Dizziness	severe, 5.5% Disc. AE	125 mg 6 times / day multiple, oral Recommended Dose: 125 mg, 6 times / day Route: oral Route: multiple Dose: 125 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13817990 Page: p.149/433	unhealthy n = 18 Health Status: unhealthy Condition: Chronic simple glaucoma Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/13817990 Page: p.149/433
Generalized eruption	severe, 5.5% Disc. AE	125 mg 6 times / day multiple, oral Recommended Dose: 125 mg, 6 times / day Route: oral Route: multiple Dose: 125 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13817990 Page: p.149/433	unhealthy n = 18 Health Status: unhealthy Condition: Chronic simple glaucoma Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/13817990 Page: p.149/433
Muscle cramps	severe, 5.5% Disc. AE	125 mg 6 times / day multiple, oral Recommended Dose: 125 mg, 6 times / day Route: oral Route: multiple Dose: 125 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13817990 Page: p.149/433	unhealthy n = 18 Health Status: unhealthy Condition: Chronic simple glaucoma Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/13817990 Page: p.149/433

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 599

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
BK channel 4	activator 214 Sources: https://pubmed.ncbi.nlm.nih.gov/23874973/	yes [EC50 5.8 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10991988/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:101096	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:101096
MolPort	MolPort-003-666-681	https://www.molport.com/shop/molecule-link/MolPort-003-666-681
ZINC	ZINC000000056721	http://zinc15.docking.org/substances/ZINC000000056721
eMolecules	498393	https://www.emolecules.com/cgi-bin/more?vid=498393

PubMed

Title	Date	PubMed
Ionic mechanisms of GABA-induced long-term potentiation in the rat superior colliculus.	2001 Oct	11685402
Transepithelial sulfate transport by avian renal proximal tubule epithelium in primary culture.	2002 Dec	12388445
Potassium drives daily reversible thallus enlargement in the marine red alga Porphyra leucosticta (Rhodophyta).	2002 Mar	11882945
Inorganic carbon limitation induces transcripts encoding components of the CO(2)-concentrating mechanism in Synechococcus sp. PCC7942 through a redox-independent pathway.	2003 Dec	14645730
Theoretical study of gas-phase acidity, pKa, lipophilicity, and solubility of some biologically active sulfonamides.	2004 Oct 15	15388166
Transport activity of MCT1 expressed in Xenopus oocytes is increased by interaction with carbonic anhydrase.	2005 Dec 2	16174776
Modulation of carbonic anhydrase activity in two nitrogen fixing cyanobacteria, Nostoc calcicola and Anabaena sp.	2005 Oct	16255166
Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides.	2005 Sep 1	16039848
Expression, purification, kinetic, and structural characterization of an alpha-class carbonic anhydrase from Aedes aegypti (AaCA1).	2006 Aug	16920039
Effect of human carbonic anhydrase II on the activity of the human electrogenic Na/HCO3 cotransporter NBCe1-A in Xenopus oocytes.	2006 Jul 14	16687407
The development of topically acting carbonic anhydrase inhibitors as anti-glaucoma agents.	2007	17504129
Inhibition of hypoxia-induced calcium responses in pulmonary arterial smooth muscle by acetazolamide is independent of carbonic anhydrase inhibition.	2007 Apr	17209136
Acclimation of wild-type cells and CO2-insensitive mutants of the green alga Chlorella ellipsoidea to elevated [CO2].	2007 Aug	17617822
Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides.	2007 Dec 1	17826101
Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy.	2007 Dec 3	17955049
Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy.	2007 Feb 15	17124262
Multiple sources of carbonic anhydrase activity in pea thylakoids: soluble and membrane-bound forms.	2007 Jan	17347907
Pulmonary vasodilation by acetazolamide during hypoxia is unrelated to carbonic anhydrase inhibition.	2007 Jan	16936246
Carbonic anhydrase inhibitors. DNA cloning, characterization, and inhibition studies of the human secretory isoform VI, a new target for sulfonamide and sulfamate inhibitors.	2007 Jan 25	17228881
Electrical parameters and ion species for active transport in human esophageal stratified squamous epithelium and Barrett's specialized columnar epithelium.	2007 Jul	17431220
Carbonic anhydrase inhibitors: the beta-carbonic anhydrase from Helicobacter pylori is a new target for sulfonamide and sulfamate inhibitors.	2007 Jul 1	17482815
Carbonic anhydrase II increases the activity of the human electrogenic Na+/HCO3- cotransporter.	2007 May 4	17353189
The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents.	2008	18336310
The alpha and beta classes carbonic anhydrases from Helicobacter pylori as novel drug targets.	2008	18336307
Carbonic anhydrase inhibitors: the X-ray crystal structure of ethoxzolamide complexed to human isoform II reveals the importance of thr200 and gln92 for obtaining tight-binding inhibitors.	2008 Apr 15	18359629
Fluid and osmolyte recovery in the common pond snail Lymnaea stagnalis following full-body withdrawal.	2008 Feb	18203987
Isolation and characterization of a gene encoding carbonic anhydrase from Ostertagia ostertagi and quantitative measurement of expression during in vivo exsheathment.	2008 Jun 14	18400401
Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties.	2009 Feb 17	19170619
Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides.	2009 Jul 15	19520577
Measurement of nanomolar dissociation constants by titration calorimetry and thermal shift assay - radicicol binding to Hsp90 and ethoxzolamide binding to CAII.	2009 Jun 10	19582223
Manganese-dependent carboanhydrase activity of photosystem II proteins.	2009 May	19538124
Carbonic anhydrase inhibitors. Cloning, characterization, and inhibition studies of a new beta-carbonic anhydrase from Mycobacterium tuberculosis.	2009 May 14	19338333
Saccharomyces cerevisiae β-carbonic anhydrase: inhibition and activation studies.	2010	20819061
Cyclodextrins in delivery systems: Applications.	2010 Apr	21814436
T tubules and surface membranes provide equally effective pathways of carbonic anhydrase-facilitated lactic acid transport in skeletal muscle.	2010 Dec 13	21179203
Ocular inserts - Advancement in therapy of eye diseases.	2010 Jul	22247860
Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption--implications for osteoclast quality.	2010 Jun 1	20515459
Cloning, characterization, and inhibition studies of a beta-carbonic anhydrase from Brucella suis.	2010 Mar 11	20158185
Carbonic anhydrase II regulates differentiation of ameloblasts via intracellular pH-dependent JNK signaling pathway.	2010 Nov	20533306

Patents

Sample Use Guides

In Vivo Use Guide

Ethoxzolamide tablets are indicated for oral administration. For treatment of glaucoma, ethoxzolamide was used at 62.5 mg. b.i.d.

Route of Administration: Oral

In Vitro Use Guide

Inhibition of human carbonic anhydrases was measured using a stop-floww assay monitoring the physiological reaction (CO2 hydration to bicarbonate). Ethoxzolamide is a relatively non-selective carbonic anhydrase (CA) inhibitor. It inhibits CA I, II, IV, VA, VB, VII, IX, XII, XIV with Ki 0.8-93 nM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:11:20 GMT 2023` Edited by `admin` on `Fri Dec 15 15:11:20 GMT 2023`
Record UNII	Z52H4811WX
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ETHOXZOLAMIDE

Common Name

English

ETHOXZOLAMIDE [ORANGE BOOK]

Common Name

English

CARDRASE

Brand Name

English

Ethoxzolamide [WHO-DD]

Common Name

English

2-BENZOTHIAZOLESULFONAMIDE, 6-ETHOXY-

Systematic Name

English

NSC-10679

Code

English

ETHOXZOLAMIDE [HSDB]

Common Name

English

ETHAMIDE

Brand Name

English

6-Ethoxy-2-benzothiazolesulfonamide

Systematic Name

English

ETHOXZOLAMIDE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29577