Diclofenamide

Identification

Name
Diclofenamide
Accession Number
DB01144
Description

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

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 305.159
Monoisotopic: 303.914603484
Chemical Formula
C6H6Cl2N2O4S2
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

Pharmacology

Indication

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

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Dichlorphenamide 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 action

Carbonic 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.

TargetActionsOrganism
ACarbonic anhydrase 2
inhibitor
Humans
ACarbonic anhydrase 1
inhibitor
Humans
ACarbonic anhydrase 4
inhibitor
Humans
ACarbonic anhydrase 7
inhibitor
Humans
UCarbonic anhydrase 3
inhibitor
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

55%

Metabolism
Not Available
Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirDiclofenamide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AcarboseThe therapeutic efficacy of Acarbose can be increased when used in combination with Diclofenamide.
AcebutololThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Acebutolol.
AceclofenacDiclofenamide may increase the excretion rate of Aceclofenac which could result in a lower serum level and potentially a reduction in efficacy.
AcemetacinThe therapeutic efficacy of Diclofenamide can be decreased when used in combination with Acemetacin.
AcetaminophenDiclofenamide may increase the excretion rate of Acetaminophen which could result in a lower serum level and potentially a reduction in efficacy.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Diclofenamide.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be increased when used in combination with Diclofenamide.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Diclofenamide which could result in a higher serum level.
AclidiniumDiclofenamide may increase the excretion rate of Aclidinium which could result in a lower serum level and potentially a reduction in efficacy.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Increase consumption of potassium-rich foods. Diclofenamide may cause hypokalemia, therefore consuming more potassium-rich foods may help prevent hypokalemia.

Products

International/Other Brands
Oratrol (Alcon)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DaranideTablet50 mg/1OralTaro Pharmaceuticals U.S.A., Inc.2012-03-162020-01-17Us
KeveyisTablet50 mg/1OralStrongbridge Us Inc.2015-08-07Not applicableUs
KeveyisTablet50 mg/1OralTaro Pharmaceuticals U.S.A., Inc.2015-08-07Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
G01AE10 — Combinations of sulfonamidesS01EC02 — Diclofenamide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
Benzenesulfonyl compounds / Dichlorobenzenes / Organosulfonamides / Aryl chlorides / Aminosulfonyl compounds / Organochlorides / Organic oxides / Organic nitrogen compounds / Hydrocarbon derivatives
Substituents
1,2-dichlorobenzene / Aminosulfonyl compound / Aromatic homomonocyclic compound / Aryl chloride / Aryl halide / Benzenesulfonamide / Benzenesulfonyl group / Chlorobenzene / Halobenzene / Hydrocarbon derivative
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
sulfonamide, dichlorobenzene (CHEBI:101085)

Chemical Identifiers

UNII
VVJ6673MHY
CAS number
120-97-8
InChI Key
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

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]
Human Metabolome Database
HMDB0015275
KEGG Drug
D00518
KEGG Compound
C07459
PubChem Compound
3038
PubChem Substance
46505039
ChemSpider
2930
BindingDB
10883
RxNav
3353
ChEBI
101085
ChEMBL
CHEMBL17
ZINC
ZINC000000896918
Therapeutic Targets Database
DAP000601
PharmGKB
PA164745512
PDBe Ligand
I7A
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dichlorphenamide
PDB Entries
2pou

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentHypokalemic Periodic Paralysis / Paralysis, Hyperkalemic Periodic1
3CompletedTreatmentHypokalemic Periodic Paralysis / Paralysis, Hyperkalemic Periodic / Paramyotonia Congenita1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral50 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)228.5Schultz,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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Details
1. Carbonic anhydrase 2
Kind
Protein
Organism
Humans
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 in...
Gene Name
CA2
Uniprot ID
P00918
Uniprot Name
Carbonic anhydrase 2
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]
Details
2. Carbonic anhydrase 1
Kind
Protein
Organism
Humans
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
Uniprot Name
Carbonic anhydrase 1
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]
Details
3. Carbonic anhydrase 4
Kind
Protein
Organism
Humans
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 an...
Gene Name
CA4
Uniprot ID
P22748
Uniprot Name
Carbonic anhydrase 4
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]
Details
4. Carbonic anhydrase 7
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide.
Gene Name
CA7
Uniprot ID
P43166
Uniprot Name
Carbonic anhydrase 7
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]
Details
5. Carbonic anhydrase 3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide.
Gene Name
CA3
Uniprot ID
P07451
Uniprot Name
Carbonic anhydrase 3
Molecular Weight
29557.215 Da
References
  1. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [PubMed:17826101]

Drug created on June 13, 2005 07:24 / Updated on June 12, 2020 10:51

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