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Identification
Name Acetazolamide
Accession Number DB00819 (APRD00119, EXPT00604)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Acetamidothiadiazolesulfonamide
  • Acetazolamid
  • Acetazolamide Sodium
  • Acetazolamine
  • Acetazoleamide
  • Acetozalamide
  • Carbonic Anhydrase Inhibitor 6063
Brand names
  • Acetamox
  • Acetazolam
  • Ak-Zol
  • Apo-Acetazolamide
  • Atenezol
  • Cidamex
  • Dazamide
  • Defiltran
  • Dehydratin
  • Diacarb
  • Diakarb
  • Diamox
  • Diamox Sequels
  • Didoc
  • Diluran
  • Diuramid
  • Diureticum-Holzinger
  • Diuriwas
  • Diutazol
  • Donmox
  • Duiramid
  • Edemox
  • Eumicton
  • Fonurit
  • Glaupax
  • Glupax
  • Natrionex
  • Nephramid
  • Nephramide
  • Phonurit
  • Sk-Acetazolamide
  • Storzolamide
  • Vetamox
Brand name mixtures Not Available
Categories
  • Anticonvulsants
  • Diuretics
  • Carbonic Anhydrase Inhibitors
CAS number 59-66-5
Weight Average: 222.245
Monoisotopic: 221.988131458
Chemical Formula C4H6N4O3S2
InChI Key InChIKey=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)
Plain Text
IUPAC Name
N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide
SMILES
CC(=O)NC1=NN=C(S1)S(N)(=O)=O
Plain Text
Mass Spec show (8.8 KB)
Taxonomy
Kingdom Not Available
Classes
  • Amino Ketones
  • Thiadiazoles
  • Sulfonyls
  • Carboxylic Acids and Derivatives
  • Sulfonamides
Substructures
  • Amino Ketones
  • Thiadiazoles
  • Sulfonyls
  • Carboxylic Acids and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Sulfonamides
Pharmacology
Indication For adjunctive treatment of: edema due to congestive heart failure; drug-induced edema; centrencephalic epilepsies; chronic simple (open-angle) glaucoma
Pharmacodynamics Acetazolamide 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 action The 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding 98%
Metabolism
Route of elimination Not Available
Half life 3 to 9 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
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
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Acetazolamide sod 500 mg vial 51.75 USD vial
Diamox Sequels 500 mg 12 Hour Capsule 5.49 USD capsule
Diamox sequels er 500 mg capsule 5.24 USD capsule
Acetazolamide powder 4.53 USD g
AcetaZOLAMIDE 500 mg 12 Hour Capsule 4.46 USD capsule
Acetazolamide 125 mg tablet 0.37 USD tablet
Acetazolamide 250 mg tablet 0.35 USD tablet
Apo-Acetazolamide 250 mg Tablet 0.13 USD tablet
Patents Not Available
Properties
State solid
Melting point 260.5 oC
Experimental Properties
Property Value Source
water solubility 0.98 mg/mL at 30 oC [YALKOWSKY,SH & DANNENFELSER,RM (1992)] PhysProp
logP -0.26 [HANSCH,C ET AL. (1995)] PhysProp
logS -2.36 [ADME Research, USCD] PhysProp
pKa 7.2 Various sources
Predicted Properties
Property Value Source
water solubility 2.79e+00 g/l ALOGPS
logP -0.39 ALOGPS
logP -1.04 ChemAxon Molconvert
logS -1.90 ALOGPS
pKa 10.35 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 115.04 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 47.36 ChemAxon Molconvert
polarizability 19.16 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00218 Link_out
KEGG Compound C06805 Link_out
PubChem Compound 1986 Link_out
PubChem Substance 46504493 Link_out
ChemSpider 1909 Link_out
BindingDB 10880 Link_out
ChEBI 27690 Link_out
ChEMBL 27690 Link_out
Therapeutic Targets Database DAP000600 Link_out
PharmGKB PA448018 Link_out
HET AZM Link_out
Drug Product Database 545015 Link_out
RxList http://www.rxlist.com/cgi/generic/aceta.htm Link_out
Drugs.com http://www.drugs.com/cdi/acetazolamide.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Acetazolamide Link_out
ATC Codes
  • S01EC01
AHFS Codes
  • 52:10.00
PDB Entries
FDA label show (148.5 KB)
MSDS show (73.4 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Drink plenty of liquids.
  • Take with food; at least 6 hours before bedtime.
Targets

1. Carbonic anhydrase 1

Pharmacological action: yes
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P00915 Link_out
Gene: CA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: Q9ULX7 Link_out
Gene: CA14 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P00918 Link_out
Gene: CA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P07451 Link_out
Gene: CA3 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4

Organism class: human
UniProt ID: P22748 Link_out
Gene: CA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P43166 Link_out
Gene: CA7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: inhibitor

Forms a water-specific channel that provides the plasma membranes of red cells and kidney proximal tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient

Organism class: human
UniProt ID: P29972 Link_out
Gene: AQP1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 3A4

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Transporters

1. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 24, 2010 12:30

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.