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Identification
NameDorzolamide
Accession NumberDB00869  (APRD00577, DB04507)
TypeSmall Molecule
GroupsApproved
Description

Dorzolamide is a carbonic anhydrase (CA) inhibitor. It is used in ophthalmic solutions (Trusopt) to lower intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension.

Structure
Thumb
Synonyms
SynonymLanguageCode
(4S-trans)-4-(ETHYLAMINO)-5,6-dihydro-6-methyl-4H-thieno(2,3-b)thiopyran-2-sulfonamide-7,7-dioxideNot AvailableNot Available
(4S,6S)-4-Ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda*6*-thieno[2,3-b]thiopyran-2-sulfonic acid amideNot AvailableNot Available
(4S,trans)-4-(Ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxideNot AvailableNot Available
4-Ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda*6*-thieno[2,3-b]thiopyran-2-sulfonic acid amideNot AvailableNot Available
4-Ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda6-thieno[2,3-b]thiopyran-2-sulfonic acid amideNot AvailableNot Available
4S,6S-DorzolamideNot AvailableNot Available
DorzolamidGermanINN
DorzolamidaSpanishINN
DorzolamideFrenchINN
DorzolamidumLatinINN
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Trusoptsolution20 mg/mLophthalmicMerck Sharp & Dohme Corp.1994-12-09Not AvailableUs
Dorzolamide Hydrochloridesolution20 mg/mLophthalmicPrasco Laboratories1994-12-09Not AvailableUs
Trusoptsolution20 mgophthalmicMerck Canada IncNot AvailableNot AvailableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dorzolamide Hydrochloridesolution20 mg/mLophthalmicTeva Pharmaceuticals USA Inc2010-01-28Not AvailableUs
Dorzolamide Hydrochloridesolution/ drops20 mg/mLophthalmicHi Tech Pharmacal Co., Inc.2008-10-28Not AvailableUs
Dorzolamide Hydrochloridesolution/ drops20 mg/mLophthalmicREMEDYREPACK INC.2013-11-18Not AvailableUs
Dorzolamide Hydrochloridesolution/ drops20 mg/mLophthalmicREMEDYREPACK INC.2014-01-09Not AvailableUs
Dorzolamide Hydrochloridesolution/ drops20 mg/mLophthalmicSandoz Inc.2009-06-01Not AvailableUs
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixtures
Brand NameIngredients
CosoptDorzolamide (Dorzolamide Hydrochloride) + Timolol (Timolol Maleate)
Salts
Name/CASStructureProperties
Dorzolamide Hydrochloride
ThumbNot applicableDBSALT000931
CategoriesNot Available
CAS number120279-96-1
WeightAverage: 324.44
Monoisotopic: 324.02721908
Chemical FormulaC10H16N2O4S3
InChI KeyIAVUPMFITXYVAF-XPUUQOCRSA-N
InChI
InChI=1S/C10H16N2O4S3/c1-3-12-8-4-6(2)18(13,14)10-7(8)5-9(17-10)19(11,15)16/h5-6,8,12H,3-4H2,1-2H3,(H2,11,15,16)/t6-,8-/m0/s1
IUPAC Name
(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ⁶-thieno[2,3-b]thiopyran-6-sulfonamide
SMILES
CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S2)S(N)(=O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 2,3,5-trisubstituted thiophenes. These are organic compounds containing a thiophene that is trisubstituted at the C-2, C3- and C5-positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassThiophenes
Sub Class2,3,5-trisubstituted thiophenes
Direct Parent2,3,5-trisubstituted thiophenes
Alternative Parents
Substituents
  • 2,3,5-trisubstituted thiophene
  • Aralkylamine
  • Thiopyran
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfone
  • Sulfonamide
  • Secondary amine
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Also used prophylatically for the inhibition of perioperative IOP increase (before neodynium yttrium aluminum garnet laser posterior capsulotomy).
PharmacodynamicsDorzolamide is topical CA inhibitor that is indicated for the reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to beta-blockers. Dorzolamide reduces IOP by approximately 17-23% in patients with elevater IOP.
Mechanism of actionDorzolamide is a sulfonamide and a highly specific carbonic anhydrase II (CA-II) inhibitor, which is the main CA isoenzyme involved in aqueous humor secretion. Inhibition of CA-II in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. Dorzolamide also accumulates in red blood cells as a result of CA-II binding, as CA-II is found predominantly in erythrocytes. However, sufficient CA-II activity remains so that adverse effects due to systemic CA inhibition are not observed.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding~33%
Metabolism
Route of eliminationDorzolamide is primarily excreted unchanged in the urine; the metabolite also is excreted in urine.
Half life4 months
ClearanceNot Available
ToxicityDizziness, headache, shortness of breath, slow heartbeat, severe asthma, cardiac arrest
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+0.9944
Blood Brain Barrier+0.6697
Caco-2 permeable-0.6627
P-glycoprotein substrateSubstrate0.5389
P-glycoprotein inhibitor INon-inhibitor0.8855
P-glycoprotein inhibitor IINon-inhibitor0.8398
Renal organic cation transporterNon-inhibitor0.9011
CYP450 2C9 substrateNon-substrate0.7755
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5096
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 substrateNon-inhibitor0.9071
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateNon-inhibitor0.9026
CYP450 3A4 substrateNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7547
Ames testNon AMES toxic0.6397
CarcinogenicityNon-carcinogens0.6933
BiodegradationNot ready biodegradable0.9946
Rat acute toxicity2.2365 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9446
hERG inhibition (predictor II)Non-inhibitor0.8706
Pharmacoeconomics
Manufacturers
  • Alcon inc
  • Apotex inc
  • Bausch and lomb inc
  • Hi tech pharmacal co inc
  • Pharmaforce inc
  • Sandoz canada inc
  • Teva pharmaceuticals usa
  • Merck research laboratories div merck co inc
Packagers
Dosage forms
FormRouteStrength
Solutionophthalmic20 mg
Solutionophthalmic20 mg/mL
Solution/ dropsophthalmic20 mg/mL
Prices
Unit descriptionCostUnit
Trusopt 2% Solution 10ml79.25USD bottle
Dorzolamide HCl 2% Solution 10ml Bottle69.42USD bottle
Dorzolamide hcl 2% eye drops6.86USD ml
Trusopt 2% eye drops6.73USD ml
Trusopt (Preservative-Free) 2 % Solution3.93USD ml
Trusopt 2 % Solution3.93USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada13292111994-05-032011-05-03
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point283-285 °CNot Available
logP-1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.699 mg/mLALOGPS
logP-0.5ALOGPS
logP-0.15ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)8.18ChemAxon
pKa (Strongest Basic)7.14ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area106.33 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity72.46 m3·mol-1ChemAxon
Polarizability31.55 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Laszlo Kovacs, Csaba Szabo, Erika Molnarne, Adrienne Kovacsne-Mezei, Claude Singer, Judith Aronhime, “Method of making dorzolamide hydrochloride.” U.S. Patent US20060155132, issued July 13, 2006.

US20060155132
General Reference
  1. Plummer CE, MacKay EO, Gelatt KN: Comparison of the effects of topical administration of a fixed combination of dorzolamide-timolol to monotherapy with timolol or dorzolamide on IOP, pupil size, and heart rate in glaucomatous dogs. Vet Ophthalmol. 2006 Jul-Aug;9(4):245-9. Pubmed
  2. Grover S, Apushkin MA, Fishman GA: Topical dorzolamide for the treatment of cystoid macular edema in patients with retinitis pigmentosa. Am J Ophthalmol. 2006 May;141(5):850-8. Epub 2006 Mar 20. Pubmed
  3. Almeida GC Jr, Faria e Souza SJ: Effect of topical dorzolamide on rabbit central corneal thickness. Braz J Med Biol Res. 2006 Feb;39(2):277-81. Epub 2006 Feb 2. Pubmed
  4. Martens-Lobenhoffer J, Banditt P: Clinical pharmacokinetics of dorzolamide. Clin Pharmacokinet. 2002;41(3):197-205. Pubmed
  5. Balfour JA, Wilde MI: Dorzolamide. A review of its pharmacology and therapeutic potential in the management of glaucoma and ocular hypertension. Drugs Aging. 1997 May;10(5):384-403. Pubmed
  6. Ponticello GS, Sugrue MF, Plazonnet B, Durand-Cavagna G: Dorzolamide, a 40-year wait. From an oral to a topical carbonic anhydrase inhibitor for the treatment of glaucoma. Pharm Biotechnol. 1998;11:555-74. Pubmed
External Links
ATC CodesS01EC03
AHFS Codes
  • 52:10.00
PDB Entries
FDA labelDownload (569 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
BrinzolamideAs both brinzolamide and dorzolamide 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.
Food InteractionsNot Available

Targets

1. Carbonic anhydrase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 2 P00918 Details

References:

  1. Lachmann C, Jorg KM, Trinkmann R: [Postoperative behavior of intraocular pressure after posterior Nd:YAG laser capsulotomy—critical evaluation in preventive administration of local carbonic anhydrase II inhibitor dorzolamide hydrochloride (Trusopt)] Klin Monatsbl Augenheilkd. 1998 Dec;213(6):326-30. Pubmed
  2. Wong BK, Bruhin PJ, Barrish A, Lin JH: Nonlinear dorzolamide pharmacokinetics in rats: concentration-dependent erythrocyte distribution and drug-metabolite displacement interaction. Drug Metab Dispos. 1996 Jun;24(6):659-63. Pubmed
  3. Berg JT, Ramanathan S, Gabrielli MG, Swenson ER: Carbonic anhydrase in mammalian vascular smooth muscle. J Histochem Cytochem. 2004 Aug;52(8):1101-6. Pubmed
  4. Hasegawa T, Hara K, Hata S: Binding of dorzolamide and its metabolite, N-deethylated dorzolamide, to human erythrocytes in vitro. Drug Metab Dispos. 1994 May-Jun;22(3):377-82. Pubmed
  5. Maren TH, Conroy CW, Wynns GC, Levy NS: Ocular absorption, blood levels, and excretion of dorzolamide, a topically active carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1997 Feb;13(1):23-30. Pubmed
  6. Sugrue MF: Pharmacological and ocular hypotensive properties of topical carbonic anhydrase inhibitors. Prog Retin Eye Res. 2000 Jan;19(1):87-112. Pubmed
  7. Sugrue MF: The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1996 Fall;12(3):363-76. Pubmed
  8. Srinivas SP, Ong A, Zhai CB, Bonanno JA: Inhibition of carbonic anhydrase activity in cultured bovine corneal endothelial cells by dorzolamide. Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3273-8. Pubmed
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Carbonic anhydrase 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 4 P22748 Details

References:

  1. Sugrue MF: The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1996 Fall;12(3):363-76. Pubmed

3. Carbonic anhydrase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 1 P00915 Details

References:

  1. Hasegawa T, Hara K, Hata S: Binding of dorzolamide and its metabolite, N-deethylated dorzolamide, to human erythrocytes in vitro. Drug Metab Dispos. 1994 May-Jun;22(3):377-82. Pubmed
  2. Maren TH, Conroy CW, Wynns GC, Levy NS: Ocular absorption, blood levels, and excretion of dorzolamide, a topically active carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1997 Feb;13(1):23-30. Pubmed
  3. Sugrue MF: The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1996 Fall;12(3):363-76. Pubmed

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

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

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12