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Identification
NameAcetazolamide
Accession NumberDB00819  (APRD00119, EXPT00604)
Typesmall molecule
Groupsapproved
Description

One of the carbonic anhydrase inhibitors that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)

Structure
Thumb
Synonyms
SynonymLanguageCode
AcetazolamidGerman INN
Acetazolamida SpanishINN
AcétazolamideFrenchINN
AcetazolamidumLatin INN
Salts
Name/CAS Structure Properties
Acetazolamide Sodium
1424-27-7
Thumb
  • InChI Key:
  • Monoisotopic Mass:
  • Average Mass:
DBSALT000539
Brand names
NameCompany
AcemitMedphano
AcemoxAcme
AcetakAkorn
AcetamideMicro Vision
AcetazolamaxPfoshen
AvvaIntas
AzmEthical
AzolNew Chemical
AzomidAdcock Ingram Pharmaceuticals
CarbinibEdol
DéfiltranCSP
DefiltranNot Available
DiaboRaymos
DiacarbPolpharma
DiamoxSanofi Aventis
Diamox DepotGoldshield
Diamox SequelsNot Available
DiazomidSanofi-Aventis
DiluranZentiva
DiuramidPolpharma
EdemoxChiesi
GlaumoxPhebra
GlaupaxOmnivision
GlupaxPhebra
Huma-ZolamideTeva
Iopar-SRFDC
MedenePharmaland
OcultenAcromax
ÖdeminSanten
UramoxTaro
ZolmideVista Pharma
Brand mixturesNot Available
Categories
CAS number59-66-5
WeightAverage: 222.245
Monoisotopic: 221.988131458
Chemical FormulaC4H6N4O3S2
InChI KeyInChIKey=BZKPWHYZMXOIDC-UHFFFAOYSA-N
InChI
InChI=1S/C4H6N4O3S2/c1-2(9)6-3-7-8-4(12-3)13(5,10)11/h1H3,(H2,5,10,11)(H,6,7,9)
IUPAC Name
N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide
SMILES
CC(=O)NC1=NN=C(S1)S(N)(=O)=O
Mass Specshow(8.82 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassAzoles
SubclassThiadiazoles
Direct parentAminothiadiazoles
Alternative parentsSulfonyls; Sulfonamides; Secondary Carboxylic Acid Amides; Polyamines; Enolates; Carboxylic Acids
Substituentssulfonic acid derivative; sulfonyl; sulfonamide; secondary carboxylic acid amide; carboxamide group; carboxylic acid derivative; polyamine; enolate; carboxylic acid; amine; organonitrogen compound
Classification descriptionThis compound belongs to the aminothiadiazoles. These are thiadiazoles with an amino group attached to the thiadiazole ring.
Pharmacology
IndicationFor adjunctive treatment of: edema due to congestive heart failure; drug-induced edema; centrencephalic epilepsies; chronic simple (open-angle) glaucoma
PharmacodynamicsAcetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion, in the treatment of certain convulsive disorders and in the promotion of diuresis in instances of abnormal fluid retention. Acetazolamide is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides.
Mechanism of actionThe anticonvulsant activity of Acetazolamide may depend on a direct inhibition of carbonic anhydrase in the CNS, which decreases carbon dioxide tension in the pulmonary alveoli, thus increasing arterial oxygen tension. The diuretic effect depends on the inhibition of carbonic anhydrase, causing a reduction in the availability of hydrogen ions for active transport in the renal tubule lumen. This leads to alkaline urine and an increase in the excretion of bicarbonate, sodium, potassium, and water.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding98%
Metabolism
Route of eliminationNot Available
Half life3 to 9 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 + 0.9156
Blood Brain Barrier + 0.9382
Caco-2 permeable - 0.7761
P-glycoprotein substrate Non-substrate 0.8369
P-glycoprotein inhibitor I Non-inhibitor 0.9267
P-glycoprotein inhibitor II Non-inhibitor 0.9507
Renal organic cation transporter Non-inhibitor 0.9365
CYP450 2C9 substrate Non-substrate 0.7316
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.7817
CYP450 1A2 substrate Non-inhibitor 0.9259
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9625
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.9037
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8798
Ames test Non AMES toxic 0.8445
Carcinogenicity Non-carcinogens 0.802
Biodegradation Not ready biodegradable 0.9301
Rat acute toxicity 1.8939 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9926
hERG inhibition (predictor II) Non-inhibitor 0.9449
Pharmacoeconomics
Manufacturers
  • Zydus pharmaceuticals usa inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Alra laboratories inc
  • Ascot hosp pharmaceuticals inc div travenol laboratories inc
  • Lannett co inc
  • Mutual pharmaceutical co inc
  • Taro pharmaceutical industries ltd
  • Vangard laboratories inc div midway medical co
  • Watson laboratories inc
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • X gen pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Acetazolamide sod 500 mg vial51.75USDvial
Diamox Sequels 500 mg 12 Hour Capsule5.49USDcapsule
Diamox sequels er 500 mg capsule5.24USDcapsule
Acetazolamide powder4.53USDg
AcetaZOLAMIDE 500 mg 12 Hour Capsule4.46USDcapsule
Acetazolamide 125 mg tablet0.37USDtablet
Acetazolamide 250 mg tablet0.35USDtablet
Apo-Acetazolamide 250 mg Tablet0.13USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point260.5 °CPhysProp
water solubility980 mg/L (at 30 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-0.26HANSCH,C ET AL. (1995)
logS-2.36ADME Research, USCD
pKa7.2MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
water solubility2.79e+00 g/lALOGPS
logP-0.39ALOGPS
logP-1ChemAxon
logS-1.9ALOGPS
pKa (strongest acidic)6.93ChemAxon
pKa (strongest basic)-3.3ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count2ChemAxon
polar surface area115.04ChemAxon
rotatable bond count2ChemAxon
refractivity47.36ChemAxon
polarizability19.16ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Angela C. Potts, Mark Gibson, “Stable ophthalmic preparations containing acetazolamide.” U.S. Patent US4888168, issued August, 1981.

US4888168
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00218
KEGG CompoundC06805
PubChem Compound1986
PubChem Substance46504493
ChemSpider1909
BindingDB10880
ChEBI27690
ChEMBLCHEMBL20
Therapeutic Targets DatabaseDAP000600
PharmGKBPA448018
HETAZM
Drug Product Database545015
RxListhttp://www.rxlist.com/cgi/generic/aceta.htm
Drugs.comhttp://www.drugs.com/cdi/acetazolamide.html
WikipediaAcetazolamide
ATC CodesS01EC01
AHFS Codes
  • 52:10.00
PDB Entries
FDA labelshow(149 KB)
MSDSshow(73.4 KB)
Interactions
Drug Interactions
Drug
Acetylsalicylic acidAcetylsalicylic acid at high dose increases the effect of the carbonic anhydrase inhibitor, acetazolamide.
Bismuth SubsalicylateThe salicylate, bismuth subsalicylate, at high dose increases the effect of the carbonic anhydrase inhibitor, acetazolamide.
BrinzolamideAs both brinzolamide and acetazolamide are carbonic anhydrase inhibitors, there is an increased risk of adverse effects.The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Avoid concurrent use of different carbonic anhydrase inhibitors when possible.
CyclosporineAcetazolamide may increase the effect and toxicity of cyclosporine.
MemantinePossible increased levels of memantine
TobramycinIncreased risk of nephrotoxicity
TopiramateAdditive renal carbonic anhydrase inhibition may occur increasing the risk of crystaluria and renal calculi. Increased risk of nephrolithiasis. Consider altnerate therapy.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
TriprolidineThe CNS depressants, Triprolidine and Acetazolamide, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Food Interactions
  • Drink plenty of liquids.
  • Take with food; at least 6 hours before bedtime.

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. Puscas I, Coltau M, Pasca R: Nonsteroidal anti-inflammatory drugs activate carbonic anhydrase by a direct mechanism of action. J Pharmacol Exp Ther. 1996 Jun;277(3):1464-6. Pubmed
  2. Meierkord H, Grunig F, Gutschmidt U, Gutierrez R, Pfeiffer M, Draguhn A, Bruckner C, Heinemann U: Sodium bromide: effects on different patterns of epileptiform activity, extracellular pH changes and GABAergic inhibition. Naunyn Schmiedebergs Arch Pharmacol. 2000 Jan;361(1):25-32. Pubmed
  3. Puscas I, Ifrim M, Maghiar T, Coltau M, Domuta G, Baican M, Hecht A: Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action. Int J Clin Pharmacol Ther. 2001 Jun;39(6):265-70. Pubmed
  4. Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. Pubmed
  5. 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
  6. 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

2. Carbonic anhydrase 14

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 14 Q9ULX7 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

3. Carbonic anhydrase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 2 P00918 Details

References:

  1. Avvaru BS, Wagner JM, Maresca A, Scozzafava A, Robbins AH, Supuran CT, McKenna R: Carbonic anhydrase inhibitors. The X-ray crystal structure of human isoform II in adduct with an adamantyl analogue of acetazolamide resides in a less utilized binding pocket than most hydrophobic inhibitors. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4376-81. Epub 2010 Jun 17. Pubmed
  2. 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 3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 3 P07451 Details

References:

  1. Avvaru BS, Wagner JM, Maresca A, Scozzafava A, Robbins AH, Supuran CT, McKenna R: Carbonic anhydrase inhibitors. The X-ray crystal structure of human isoform II in adduct with an adamantyl analogue of acetazolamide resides in a less utilized binding pocket than most hydrophobic inhibitors. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4376-81. Epub 2010 Jun 17. Pubmed

5. Carbonic anhydrase 4

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 4 P22748 Details

References:

  1. Avvaru BS, Wagner JM, Maresca A, Scozzafava A, Robbins AH, Supuran CT, McKenna R: Carbonic anhydrase inhibitors. The X-ray crystal structure of human isoform II in adduct with an adamantyl analogue of acetazolamide resides in a less utilized binding pocket than most hydrophobic inhibitors. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4376-81. Epub 2010 Jun 17. Pubmed
  2. 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

6. 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

7. Aquaporin-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Aquaporin-1 P29972 Details

References:

  1. Xiang Y, Ma B, Li T, Yu HM, Li XJ: Acetazolamide suppresses tumor metastasis and related protein expression in mice bearing Lewis lung carcinoma. Acta Pharmacol Sin. 2002 Aug;23(8):745-51. Pubmed
  2. Mu SM, Ji XH, Ma B, Yu HM, Li XJ: [Differential protein analysis in rat renal proximal tubule epithelial cells in response to acetazolamide and its relation with the inhibition of AQP1] Yao Xue Xue Bao. 2003 Mar;38(3):169-72. Pubmed
  3. Ma B, Xiang Y, Mu SM, Li T, Yu HM, Li XJ: Effects of acetazolamide and anordiol on osmotic water permeability in AQP1-cRNA injected Xenopus oocyte. Acta Pharmacol Sin. 2004 Jan;25(1):90-7. Pubmed
  4. Oshio K, Song Y, Verkman AS, Manley GT: Aquaporin-1 deletion reduces osmotic water permeability and cerebrospinal fluid production. Acta Neurochir Suppl. 2003;86:525-8. Pubmed
  5. Xiang Y, Ma B, Li T, Gao JW, Yu HM, Li XJ: Acetazolamide inhibits aquaporin-1 protein expression and angiogenesis. Acta Pharmacol Sin. 2004 Jun;25(6):812-6. Pubmed

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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

Comments
Drug created on June 13, 2005 07:24 / Updated on November 08, 2013 13:31