Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
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
DorzolamidGermanINN
DorzolamidaSpanishINN
DorzolamideFrenchINN
DorzolamidumLatinINN
Salts
Name/CAS Structure Properties
Dorzolamide Hydrochloride
Thumb Not applicable DBSALT000931
Brand names
NameCompany
TrusoptMerck
Brand mixtures
Brand NameIngredients
CosoptDorzolamide (Dorzolamide Hydrochloride) + Timolol (Timolol Maleate)
CategoriesNot Available
CAS number120279-96-1
WeightAverage: 324.44
Monoisotopic: 324.02721908
Chemical FormulaC10H16N2O4S3
InChI KeyInChIKey=IAVUPMFITXYVAF-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-1$l^{6},7-thieno[2,3-b][1$l^{6}]thiopyran-6-sulfonamide
SMILES
CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S2)S(N)(=O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassThiopyrans
SubclassNot Available
Direct parentThiopyrans
Alternative parentsThiophenes; Sulfonamides; Sulfones; Sulfoxides; Polyamines; Dialkylamines
Substituentssulfonyl; sulfonamide; thiophene; sulfonic acid derivative; sulfone; sulfoxide; polyamine; secondary amine; secondary aliphatic amine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the thiopyrans. These are compounds containing a six-member aliphatic heterocycle made up of one sulfur atom and five carbon atoms.
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
Property Value Probability
Human Intestinal Absorption + 0.9944
Blood Brain Barrier + 0.6697
Caco-2 permeable - 0.6627
P-glycoprotein substrate Substrate 0.5389
P-glycoprotein inhibitor I Non-inhibitor 0.8855
P-glycoprotein inhibitor II Non-inhibitor 0.8398
Renal organic cation transporter Non-inhibitor 0.9011
CYP450 2C9 substrate Non-substrate 0.7755
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.5096
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.831
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7547
Ames test Non AMES toxic 0.6397
Carcinogenicity Non-carcinogens 0.6933
Biodegradation Not ready biodegradable 0.9946
Rat acute toxicity 2.2365 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9446
hERG inhibition (predictor II) Non-inhibitor 0.8706
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
SolutionOphthalmic
Prices
Unit descriptionCostUnit
Trusopt 2% Solution 10ml79.25USDbottle
Dorzolamide HCl 2% Solution 10ml Bottle69.42USDbottle
Dorzolamide hcl 2% eye drops6.86USDml
Trusopt 2% eye drops6.73USDml
Trusopt (Preservative-Free) 2 % Solution3.93USDml
Trusopt 2 % Solution3.93USDml
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 solubility6.99e-01 g/lALOGPS
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 area106.33ChemAxon
rotatable bond count3ChemAxon
refractivity72.46ChemAxon
polarizability31.55ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
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
ResourceLink
KEGG DrugD07871
KEGG CompoundC06969
BindingDB50043906
ChEBI4702
ChEMBLCHEMBL218490
Therapeutic Targets DatabaseDAP000775
PharmGKBPA164748765
Drug Product Database2216205
RxListhttp://www.rxlist.com/cgi/generic/dorzolamide.htm
Drugs.comhttp://www.drugs.com/cdi/dorzolamide-drops.html
WikipediaDorzolamide
ATC CodesS01EC03
AHFS Codes
  • 52:10.00
PDB Entries
FDA labelshow(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

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

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

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