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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
1,3-disulfamoyl-4,5-dichlorobenzene
1,3-Disulfamyl-4,5-dichlorobenzene
3,4-Dichloro-5-sulfamylbenzenesulfonamide
4,5-Dichloro-1,3-benzenedisulfonamide
4,5-dichloro-1,3-disulfamoylbenzene
4,5-Dichloro-benzene-1,3-disulfonic acid diamide
4,5-dichloro-m-benzenedisulfonamide
4,5-DICHLOROBENZENE-1,3-disulfonamide
Dichlofenamide
Dichlorophenamide
Dichlorphenamide
Diclofenamida
Diclofenamide
Diclofenamidum
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Daranidetablet50 mg/1oralTaro Pharmaceuticals U.S.A., Inc.2012-03-162016-04-05Us
Keveyistablet50 mg/1oralTaro Pharmaceuticals U.S.A., Inc.2015-08-072016-04-05Us
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
OratrolAlcon
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIVVJ6673MHY
CAS number120-97-8
WeightAverage: 305.159
Monoisotopic: 303.914603484
Chemical FormulaC6H6Cl2N2O4S2
InChI KeyInChIKey=GJQPMPFPNINLKP-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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonamides
Direct ParentBenzenesulfonamides
Alternative Parents
Substituents
  • Benzenesulfonamide
  • 1,2-dichlorobenzene
  • Halobenzene
  • Chlorobenzene
  • Aryl halide
  • Aryl chloride
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organochloride
  • Organohalogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding55%
MetabolismNot Available
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
PropertyValueProbability
Human Intestinal Absorption+0.9913
Blood Brain Barrier+0.8167
Caco-2 permeable-0.54
P-glycoprotein substrateNon-substrate0.8835
P-glycoprotein inhibitor INon-inhibitor0.9593
P-glycoprotein inhibitor IINon-inhibitor0.9922
Renal organic cation transporterNon-inhibitor0.9254
CYP450 2C9 substrateNon-substrate0.8101
CYP450 2D6 substrateNon-substrate0.9085
CYP450 3A4 substrateNon-substrate0.7198
CYP450 1A2 substrateNon-inhibitor0.9044
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.957
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9691
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8017
Ames testNon AMES toxic0.7954
CarcinogenicityNon-carcinogens0.7986
BiodegradationNot ready biodegradable0.9872
Rat acute toxicity2.1828 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9697
hERG inhibition (predictor II)Non-inhibitor0.9558
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral50 mg/1
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 Solubility0.398 mg/mLALOGPS
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

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

General References
  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:10632100 ]
  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:1364383 ]
External Links
ATC CodesS01EC02
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetazolamideThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Acetazolamide.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Diclofenamide.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Diclofenamide.
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Aminosalicylic Acid is combined with Diclofenamide.
AmphetamineDiclofenamide may decrease the excretion rate of Amphetamine which could result in a lower serum level and potentially a reduction in efficacy.
BenzphetamineDiclofenamide may decrease the excretion rate of Benzphetamine which could result in a lower serum level and potentially a reduction in efficacy.
Bismuth SubsalicylateThe risk or severity of adverse effects can be increased when Bismuth Subsalicylate is combined with Diclofenamide.
BrinzolamideThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Brinzolamide.
ButabarbitalButabarbital may increase the hypotensive activities of Diclofenamide.
ButethalButethal may increase the hypotensive activities of Diclofenamide.
CaffeineThe risk or severity of adverse effects can be increased when Caffeine is combined with Diclofenamide.
CanagliflozinThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Canagliflozin.
CarbamazepineThe serum concentration of Carbamazepine can be increased when it is combined with Diclofenamide.
CathinoneDiclofenamide may decrease the excretion rate of Cathinone which could result in a lower serum level and potentially a reduction in efficacy.
DextroamphetamineDiclofenamide may decrease the excretion rate of Dextroamphetamine which could result in a lower serum level and potentially a reduction in efficacy.
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Diclofenamide.
DorzolamideThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Dorzolamide.
DuloxetineDiclofenamide may increase the orthostatic hypotensive activities of Duloxetine.
EphedrineThe serum concentration of Ephedrine can be increased when it is combined with Diclofenamide.
EthoxzolamideThe risk or severity of adverse effects can be increased when Ethoxzolamide is combined with Diclofenamide.
FlecainideThe serum concentration of Flecainide can be increased when it is combined with Diclofenamide.
FosphenytoinThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Fosphenytoin.
HeptabarbitalHeptabarbital may increase the hypotensive activities of Diclofenamide.
HexamethylenetetramineThe therapeutic efficacy of Hexamethylenetetramine can be decreased when used in combination with Diclofenamide.
HexobarbitalHexobarbital may increase the hypotensive activities of Diclofenamide.
LevodopaDiclofenamide may increase the orthostatic hypotensive activities of Levodopa.
LisdexamfetamineDiclofenamide may decrease the excretion rate of Lisdexamfetamine which could result in a lower serum level and potentially a reduction in efficacy.
LithiumThe serum concentration of Lithium can be decreased when it is combined with Diclofenamide.
Magnesium salicylateThe risk or severity of adverse effects can be increased when Magnesium salicylate is combined with Diclofenamide.
MemantineDiclofenamide may decrease the excretion rate of Memantine which could result in a lower serum level and potentially a reduction in efficacy.
MetforminThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Metformin.
MethamphetamineDiclofenamide may decrease the excretion rate of Methamphetamine which could result in a lower serum level and potentially a reduction in efficacy.
MethazolamideThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Methazolamide.
MethohexitalMethohexital may increase the hypotensive activities of Diclofenamide.
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Diclofenamide.
NicorandilNicorandil may increase the hypotensive activities of Diclofenamide.
PentobarbitalPentobarbital may increase the hypotensive activities of Diclofenamide.
PhendimetrazineDiclofenamide may decrease the excretion rate of Phendimetrazine which could result in a lower serum level and potentially a reduction in efficacy.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Diclofenamide.
PhentermineDiclofenamide may decrease the excretion rate of Phentermine which could result in a lower serum level and potentially a reduction in efficacy.
PhenytoinThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Phenytoin.
PrimidoneThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Primidone.
PseudoephedrineThe serum concentration of Pseudoephedrine can be increased when it is combined with Diclofenamide.
QuinidineDiclofenamide may decrease the excretion rate of Quinidine which could result in a lower serum level and potentially a reduction in efficacy.
RisperidoneDiclofenamide may increase the hypotensive activities of Risperidone.
SalsalateThe risk or severity of adverse effects can be increased when Salsalate is combined with Diclofenamide.
SecobarbitalSecobarbital may increase the hypotensive activities of Diclofenamide.
TopiramateThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Topiramate.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Diclofenamide.
TriethylenetetramineThe serum concentration of Triethylenetetramine can be decreased when it is combined with Diclofenamide.
TriprolidineThe serum concentration of Triprolidine can be increased when it is combined with Diclofenamide.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Diclofenamide.
ZonisamideThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Zonisamide.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular Weight:
28870.0 Da
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:14684332 ]
  2. Lindskog S: Structure and mechanism of carbonic anhydrase. Pharmacol Ther. 1997;74(1):1-20. [PubMed:9336012 ]
  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:17228881 ]
  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. doi: 10.1093/hmg/ddp358. Epub 2009 Jul 31. [PubMed:19648295 ]
  5. Cleland JC, Griggs RC: Treatment of neuromuscular channelopathies: current concepts and future prospects. Neurotherapeutics. 2008 Oct;5(4):607-12. doi: 10.1016/j.nurt.2008.09.001. [PubMed:19019313 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate ex...
Gene Name:
CA2
Uniprot ID:
P00918
Molecular Weight:
29245.895 Da
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:18336310 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
Gene Name:
CA4
Uniprot ID:
P22748
Molecular Weight:
35032.075 Da
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:18336310 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA7
Uniprot ID:
P43166
Molecular Weight:
29658.235 Da
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:18336310 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on April 11, 2014 14:59