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Identification
NameDiclofenamide
Accession NumberDB01144  (APRD00131, DB07948)
TypeSmall Molecule
GroupsApproved
Description

A carbonic anhydrase inhibitor that is used in the treatment of glaucoma. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
1,3-disulfamoyl-4,5-dichlorobenzeneNot AvailableNot Available
1,3-Disulfamyl-4,5-dichlorobenzeneNot AvailableNot Available
3,4-Dichloro-5-sulfamylbenzenesulfonamideNot AvailableNot Available
4,5-Dichloro-1,3-benzenedisulfonamideNot AvailableNot Available
4,5-dichloro-1,3-disulfamoylbenzeneNot AvailableNot Available
4,5-Dichloro-benzene-1,3-disulfonic acid diamideNot AvailableNot Available
4,5-dichloro-m-benzenedisulfonamideNot AvailableNot Available
4,5-DICHLOROBENZENE-1,3-disulfonamideNot AvailableNot Available
DichlofenamideNot AvailableINN
DichlorophenamideNot AvailableNot Available
DichlorphenamideNot AvailableNot Available
DiclofenamidaSpanishINN
DiclofenamideNot AvailableNot Available
DiclofenamidumLatinINN
SaltsNot Available
Brand names
NameCompany
DaranideTaro
OratrolAlcon
Brand mixturesNot Available
Categories
CAS number120-97-8
WeightAverage: 305.159
Monoisotopic: 303.914603484
Chemical FormulaC6H6Cl2N2O4S2
InChI KeyGJQPMPFPNINLKP-UHFFFAOYSA-N
InChI
InChI=1S/C6H6Cl2N2O4S2/c7-4-1-3(15(9,11)12)2-5(6(4)8)16(10,13)14/h1-2H,(H2,9,11,12)(H2,10,13,14)
IUPAC Name
4,5-dichlorobenzene-1,3-disulfonamide
SMILES
NS(=O)(=O)C1=CC(=C(Cl)C(Cl)=C1)S(N)(=O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentBenzenesulfonamides
Alternative parentsDichlorobenzenes; Aryl Chlorides; Sulfonyls; Sulfonamides; Polyamines; Organochlorides
Substituents1,2-dichlorobenzene; chlorobenzene; aryl halide; aryl chloride; sulfonamide; sulfonyl; sulfonic acid derivative; polyamine; organochloride; organohalogen
Classification descriptionThis compound belongs to the benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Pharmacology
IndicationFor adjunctive treatment of: chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure
PharmacodynamicsDichlorphenamide is an oral carbonic anhydrase inhibitor indicated for adjunctive treatment of: chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. Carbonic anhydrase inhibitors reduce intraocular pressure by partially suppressing the secretion of aqueous humor (inflow).
Mechanism of actionCarbonic anhydrase inhibitors reduce intraocular pressure by partially suppressing the secretion of aqueous humor (inflow), although the mechanism by which they do this is not fully understood. Evidence suggests that HCO3- ions are produced in the ciliary body by hydration of carbon dioxide under the influence of carbonic anhydrase and diffuse into the posterior chamber which contains more Na+ and HCO3- ions than does plasma and consequently is hypertonic. Water is then attracted to the posterior chamber by osmosis, resulting in a drop in pressure.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding55%
Metabolism
Route of eliminationNot Available
Half lifeNot Available
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 + 0.9913
Blood Brain Barrier + 0.8167
Caco-2 permeable - 0.54
P-glycoprotein substrate Non-substrate 0.8835
P-glycoprotein inhibitor I Non-inhibitor 0.9593
P-glycoprotein inhibitor II Non-inhibitor 0.9922
Renal organic cation transporter Non-inhibitor 0.9254
CYP450 2C9 substrate Non-substrate 0.8101
CYP450 2D6 substrate Non-substrate 0.9085
CYP450 3A4 substrate Non-substrate 0.7198
CYP450 1A2 substrate Non-inhibitor 0.9044
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Non-inhibitor 0.957
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.9691
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8017
Ames test Non AMES toxic 0.7954
Carcinogenicity Non-carcinogens 0.7986
Biodegradation Not ready biodegradable 0.9872
Rat acute toxicity 2.1828 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9697
hERG inhibition (predictor II) Non-inhibitor 0.9558
Pharmacoeconomics
Manufacturers
  • Taro pharmaceuticals usa inc
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point228.5Schultz,E.M.; U.S.Patent 2,835,702; May 20, 1958; assigned to Merck & Co.,Inc.
logP0.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.398ALOGPS
logP0.92ALOGPS
logP0.39ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)7.94ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area120.32 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity59.98 m3·mol-1ChemAxon
Polarizability25.04 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Schultz,E.M.; U.S.Patent 2,835,702; May 20, 1958; assigned to Merck & Co.,Inc.

General Reference
  1. Tawil R, McDermott MP, Brown R Jr, Shapiro BC, Ptacek LJ, McManis PG, Dalakas MC, Spector SA, Mendell JR, Hahn AF, Griggs RC: Randomized trials of dichlorphenamide in the periodic paralyses. Working Group on Periodic Paralysis. Ann Neurol. 2000 Jan;47(1):46-53. Pubmed
  2. Okada S, Izumi W, Murai M, Komatsu H, Ishimitsu S: [Diclofenamide Reference Standard (Control 891) of National Institute of Hygienic Sciences] Eisei Shikenjo Hokoku. 1991;(109):148-50. Pubmed
External Links
ResourceLink
KEGG DrugD00518
KEGG CompoundC07459
PubChem Compound3038
PubChem Substance46505039
ChemSpider2930
BindingDB10883
ChEBI101085
ChEMBLCHEMBL17
Therapeutic Targets DatabaseDAP000601
PharmGKBPA164745512
HETI7A
RxListhttp://www.rxlist.com/cgi/generic/dichlorphen.htm
Drugs.comhttp://www.drugs.com/mtm/dichlorphenamide.html
WikipediaDichlorphenamide
ATC CodesS01EC02
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
Acetylsalicylic acidAcetylsalicylic acid at high dose increases the effect of the carbonic anhydrase inhibitor, dichlorphenamide.
BrinzolamideAs both brinzolamide and dichlorphenamide 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.
MemantinePossible increased levels of memantine
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food InteractionsNot Available

Targets

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. Winum JY, Casini A, Mincione F, Starnotti M, Montero JL, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits. Bioorg Med Chem Lett. 2004 Jan 5;14(1):225-9. Pubmed
  2. Lindskog S: Structure and mechanism of carbonic anhydrase. Pharmacol Ther. 1997;74(1):1-20. Pubmed
  3. Nishimori I, Minakuchi T, Onishi S, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. DNA cloning, characterization, and inhibition studies of the human secretory isoform VI, a new target for sulfonamide and sulfamate inhibitors. J Med Chem. 2007 Jan 25;50(2):381-8. Pubmed
  4. Giacomotto J, Pertl C, Borrel C, Walter MC, Bulst S, Johnsen B, Baillie DL, Lochmuller H, Thirion C, Segalat L: Evaluation of the therapeutic potential of carbonic anhydrase inhibitors in two animal models of dystrophin deficient muscular dystrophy. Hum Mol Genet. 2009 Nov 1;18(21):4089-101. Epub 2009 Jul 31. Pubmed
  5. Cleland JC, Griggs RC: Treatment of neuromuscular channelopathies: current concepts and future prospects. Neurotherapeutics. 2008 Oct;5(4):607-12. Pubmed

2. Carbonic anhydrase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 2 P00918 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

3. Carbonic anhydrase 4

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 4 P22748 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

4. 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

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 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

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Drug created on June 13, 2005 07:24 / Updated on April 11, 2014 14:59