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Details

Stereochemistry ACHIRAL
Molecular Formula C5H8N4O3S2
Molecular Weight 236.272
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of METHAZOLAMIDE

SMILES

CN1N=C(S\C1=N\C(C)=O)S(N)(=O)=O

InChI

InChIKey=FLOSMHQXBMRNHR-QPJJXVBHSA-N
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+

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/methazolamide.html

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. 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. Methazolamide is used for treatment of chronic open-angle glaucoma and acute angle-closure glaucoma.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
50.0 nM [Ki]
14.0 nM [Ki]
27.0 nM [Ki]
3.4 nM [Ki]
2.1 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Methazolamide

Approved Use

indicated in the treatment of ocular conditions where lowering intraocular pressure is likely to be of therapeutic benefit, such as chronic open-angle glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where lowering the intraocular pressure is desired before surgery.

Launch Date

1993
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.5 μg/mL
25 mg 2 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
METHAZOLAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
5.1 μg/mL
50 mg 2 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
METHAZOLAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
10.7 μg/mL
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
METHAZOLAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1130 μg × min/mL
25 mg 2 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
METHAZOLAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
2571 μg × min/mL
50 mg 2 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
METHAZOLAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
5418 μg × min/mL
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
METHAZOLAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14 h
steady-state, oral
METHAZOLAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
45%
25 mg 2 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
METHAZOLAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 3 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, 67.5 years
n = 24
Health Status: unhealthy
Condition: Glaucoma
Age Group: 67.5 years
Sex: M+F
Population Size: 24
Sources:
Disc. AE: Loss of energy, Fatigue...
AEs leading to
discontinuation/dose reduction:
Loss of energy (2 patients)
Fatigue (2 patients)
Lethargy (2 patients)
Sources:
50 mg 2 times / day multiple, oral
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Co-administed with::
aspirin(high concentration)
Sources:
unhealthy
Disc. AE: Anorexia, Tachypnea...
AEs

AEs

AESignificanceDosePopulation
Fatigue 2 patients
Disc. AE
100 mg 3 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, 67.5 years
n = 24
Health Status: unhealthy
Condition: Glaucoma
Age Group: 67.5 years
Sex: M+F
Population Size: 24
Sources:
Lethargy 2 patients
Disc. AE
100 mg 3 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, 67.5 years
n = 24
Health Status: unhealthy
Condition: Glaucoma
Age Group: 67.5 years
Sex: M+F
Population Size: 24
Sources:
Loss of energy 2 patients
Disc. AE
100 mg 3 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, 67.5 years
n = 24
Health Status: unhealthy
Condition: Glaucoma
Age Group: 67.5 years
Sex: M+F
Population Size: 24
Sources:
Anorexia Disc. AE
50 mg 2 times / day multiple, oral
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Co-administed with::
aspirin(high concentration)
Sources:
unhealthy
Coma Disc. AE
50 mg 2 times / day multiple, oral
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Co-administed with::
aspirin(high concentration)
Sources:
unhealthy
Lethargy Disc. AE
50 mg 2 times / day multiple, oral
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Co-administed with::
aspirin(high concentration)
Sources:
unhealthy
Tachypnea Disc. AE
50 mg 2 times / day multiple, oral
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Co-administed with::
aspirin(high concentration)
Sources:
unhealthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Cysteine conjugate of methazolamide is metabolized by beta-lyase.
2001 Feb
Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the perfluorobenzoyl analogue of methazolamide. Implications for the drug design of fluorinated inhibitors.
2003 Aug
Carbonic anhydrase inhibitors. Inhibition of tumor-associated isozyme IX by halogenosulfanilamide and halogenophenylaminobenzolamide derivatives.
2003 May 22
Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits.
2004 Jan 5
Carbonic anhydrase inhibitors: the first QSAR study on inhibition of tumor-associated isoenzyme IX with aromatic and heterocyclic sulfonamides.
2004 Jun 21
Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides.
2005 Feb 15
Carbonic anhydrase inhibitors. Inhibition of the human cytosolic isozyme VII with aromatic and heterocyclic sulfonamides.
2005 Feb 15
Carbonic anhydrase inhibitors. Inhibition of the transmembrane isozyme XII with sulfonamides-a new target for the design of antitumor and antiglaucoma drugs?
2005 Feb 15
Stimulation of renal sulfate secretion by metabolic acidosis requires Na+/H+ exchange induction and carbonic anhydrase.
2005 Jul
Carbonic anhydrase in the adult mosquito midgut.
2005 Sep
Effects of low-dose methazolamide on the control of breathing in cats.
2006
Carbonic anhydrase inhibitors: DNA cloning and inhibition studies of the alpha-carbonic anhydrase from Helicobacter pylori, a new target for developing sulfonamide and sulfamate gastric drugs.
2006 Mar 23
Topical dorzolamide for the treatment of cystoid macular edema in patients with retinitis pigmentosa.
2006 May
The development of topically acting carbonic anhydrase inhibitors as anti-glaucoma agents.
2007
Statement on high-altitude illnesses. An Advisory Committee Statement (ACS).
2007 Apr 1
Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides.
2007 Dec 1
Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy.
2007 Dec 3
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
Topical inhibition of nasal carbonic anhydrase affects the CO2 detection threshold in rats.
2007 Mar
The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents.
2008
The alpha and beta classes carbonic anhydrases from Helicobacter pylori as novel drug targets.
2008
Carbonic anhydrase II and alveolar fluid reabsorption during hypercapnia.
2008 Jan
Rational use of the fixed combination of dorzolamide - timolol in the management of raised intraocular pressure and glaucoma.
2008 Jun
Recent advances in pharmacotherapy of glaucoma.
2008 Oct
QSAR studies for the inhibition of the transmembrane carbonic anhydrase isozyme XIV with sulfonamides using PRECLAV software.
2009 Apr
Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides.
2009 Jul 15
Patents

Sample Use Guides

Usual Adult Dose for Glaucoma 50 to 100 mg orally 2 or 3 times a day
Route of Administration: Oral
Methazolamide (0.1 mM) inhibited acid-induced [CO(2)](t) increase in mice.
Name Type Language
METHAZOLAMIDE
HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
INN  
Official Name English
METHAZOLAMIDE [HSDB]
Common Name English
methazolamide [INN]
Common Name English
ACETAMIDE, N-(5-(AMINOSULFONYL)-3-METHYL-1,3,4-THIADIAZOL-2(3H)-YLIDENE)-
Systematic Name English
METHAZOLAMIDE [VANDF]
Common Name English
METHAZOLAMIDE [USP-RS]
Common Name English
NEPTAZANE
Brand Name English
Acetamide, N-[5-(aminosulfonyl)-3-methyl-1,3,4-thiadiazol-2(3H)-ylidene]-, [N(E)]-
Systematic Name English
N-(4-METHYL-2-SULFAMOYL-.DELTA.(SUP 2)-1,3,4-THIADIAZOLIN-5-YLIDENE)ACETAMIDE
Common Name English
METHAZOLAMIDE [JAN]
Common Name English
Methazolamide [WHO-DD]
Common Name English
VVP808
Code English
METHAZOLAMIDE [MI]
Common Name English
NEPTAZANEAT
Common Name English
METHAZOLAMIDE [USP MONOGRAPH]
Common Name English
NSC-758426
Code English
[N(E)]-N-[5-(Aminosulfonyl)-3-methyl-1,3,4-thiadiazol-2(3H)-ylidene]acetamide
Systematic Name English
METHENAMIDE
Common Name English
VVP-808
Code English
L-584601
Code English
METHAZOLAMIDE [MART.]
Common Name English
METHAZOLAMIDE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
LIVERTOX NBK548664
Created by admin on Fri Dec 15 15:13:11 GMT 2023 , Edited by admin on Fri Dec 15 15:13:11 GMT 2023
NCI_THESAURUS C29577
Created by admin on Fri Dec 15 15:13:11 GMT 2023 , Edited by admin on Fri Dec 15 15:13:11 GMT 2023
WHO-VATC QS01EC05
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WHO-ATC S01EC05
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NCI_THESAURUS C448
Created by admin on Fri Dec 15 15:13:11 GMT 2023 , Edited by admin on Fri Dec 15 15:13:11 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID1023281
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PRIMARY
MESH
D008704
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PRIMARY
EVMPD
SUB08843MIG
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PRIMARY
RS_ITEM_NUM
1406005
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PRIMARY
DAILYMED
W733B0S9SD
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PRIMARY
CHEBI
29202
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PRIMARY
DRUG CENTRAL
1741
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PRIMARY
WIKIPEDIA
METHAZOLAMIDE
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PRIMARY
IUPHAR
6828
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PRIMARY
CAS
2101958-72-7
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ALTERNATIVE
ECHA (EC/EINECS)
209-066-7
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PRIMARY
MERCK INDEX
m7304
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PRIMARY Merck Index
ChEMBL
CHEMBL19
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PRIMARY
INN
882
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PRIMARY
NSC
758426
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PRIMARY
HSDB
3269
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PRIMARY
DRUG BANK
DB00703
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PRIMARY
RXCUI
6826
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PRIMARY RxNorm
LACTMED
Methazolamide
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PRIMARY
CAS
554-57-4
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PRIMARY
SMS_ID
100000081410
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PRIMARY
NCI_THESAURUS
C61318
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PRIMARY
FDA UNII
W733B0S9SD
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PRIMARY