DORZOLAMIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H16N2O4S3
Molecular Weight	324.44
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S2)S(N)(=O)=O

InChI

InChIKey=IAVUPMFITXYVAF-XPUUQOCRSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.merck.com/product/usa/pi_circulars/t/trusopt/trusopt_pi.pdf

Dorzolamide is a sulfonamide and a highly specific carbonic anhydrase II (CA-II) inhibitor, which is the main CA isoenzyme involved in aqueous humor secretion. Dorzolamide is marketed under the trade name Trusopt, indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. It catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In humans, carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic anhydrase II (CA-II), found primarily in red blood cells (RBCs), but also in other tissues. Inhibition of carbonic anhydrase 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. The result is a reduction in intraocular pressure (IOP). TRUSOPT Ophthalmic Solution contains dorzolamide hydrochloride, an inhibitor of human carbonic anhydrase II. Following topical ocular administration, TRUSOPT reduces elevated intraocular pressure. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Carbonic anhydrase II 88 Target ID: CHEMBL205 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020408s047lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/9029437 \| https://www.ncbi.nlm.nih.gov/pubmed/10948564	Inhibitor 8504		0.18 nM [IC50]
Carbonic anhydrase IV 33 Target ID: CHEMBL3729 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020408s047lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/9029437	Inhibitor 8504		31.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ocular hypertension 52 Sources: https://www.merck.com/product/usa/pi_circulars/t/trusopt/trusopt_pi.pdf	Primary		Approved 8583	TRUSOPT Approved Use TRUSOPT Ophthalmic Solution is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Launch Date 1994
Open-angle glaucoma 53 Sources: https://www.merck.com/product/usa/pi_circulars/t/trusopt/trusopt_pi.pdf	Primary		Approved 8583	TRUSOPT Approved Use TRUSOPT Ophthalmic Solution is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Launch Date 1994

AUC

Value	Dose	Co-administered	Analyte	Population
22667 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7720769	7.7 μg 4 times / day multiple, topical dose: 7.7 μg route of administration: Topical experiment type: MULTIPLE co-administered:		DORZOLAMIDE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
133 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7720769	7.7 μg 4 times / day multiple, topical dose: 7.7 μg route of administration: Topical experiment type: MULTIPLE co-administered:		DORZOLAMIDE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

Doses

Dose	Population	Adverse events
1 drop 3 times / day multiple, ophthalmic Highest studied dose Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/	unhealthy, 61.1 years (range: 23-83 years) Health Status: unhealthy Age Group: 61.1 years (range: 23-83 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/	Other AEs: Application site irritation, Lacrimation... Other AEs: Application site irritation (8 patients) Lacrimation (1 patient) Foreign body sensation in eyes (1 patient) Conjunctival hyperemia (1 patient) Visual disturbance (1 patient) Throat pain (1 patient) Seborrheic dermatitis (1 patient) Sugar urinary (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/
1 drop 3 times / day multiple, ophthalmic Recommended Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9715679/	unhealthy, 62.1 years (range: 20-88 years) Health Status: unhealthy Age Group: 62.1 years (range: 20-88 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/9715679/	Other AEs: Ocular stinging, Conjunctival injection... Other AEs: Ocular stinging (22%) Conjunctival injection (12%) Headache (3%) Sources: https://pubmed.ncbi.nlm.nih.gov/9715679/

AEs

AE	Significance	Dose	Population
Conjunctival hyperemia	1 patient	1 drop 3 times / day multiple, ophthalmic Highest studied dose Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/	unhealthy, 61.1 years (range: 23-83 years) Health Status: unhealthy Age Group: 61.1 years (range: 23-83 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/
Foreign body sensation in eyes	1 patient	1 drop 3 times / day multiple, ophthalmic Highest studied dose Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/	unhealthy, 61.1 years (range: 23-83 years) Health Status: unhealthy Age Group: 61.1 years (range: 23-83 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/
Lacrimation	1 patient	1 drop 3 times / day multiple, ophthalmic Highest studied dose Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/	unhealthy, 61.1 years (range: 23-83 years) Health Status: unhealthy Age Group: 61.1 years (range: 23-83 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/
Seborrheic dermatitis	1 patient	1 drop 3 times / day multiple, ophthalmic Highest studied dose Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/	unhealthy, 61.1 years (range: 23-83 years) Health Status: unhealthy Age Group: 61.1 years (range: 23-83 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/
Sugar urinary	1 patient	1 drop 3 times / day multiple, ophthalmic Highest studied dose Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/	unhealthy, 61.1 years (range: 23-83 years) Health Status: unhealthy Age Group: 61.1 years (range: 23-83 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/
Throat pain	1 patient	1 drop 3 times / day multiple, ophthalmic Highest studied dose Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/	unhealthy, 61.1 years (range: 23-83 years) Health Status: unhealthy Age Group: 61.1 years (range: 23-83 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/
Visual disturbance	1 patient	1 drop 3 times / day multiple, ophthalmic Highest studied dose Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/	unhealthy, 61.1 years (range: 23-83 years) Health Status: unhealthy Age Group: 61.1 years (range: 23-83 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/
Application site irritation	8 patients	1 drop 3 times / day multiple, ophthalmic Highest studied dose Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/	unhealthy, 61.1 years (range: 23-83 years) Health Status: unhealthy Age Group: 61.1 years (range: 23-83 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14733709/
Conjunctival injection	12%	1 drop 3 times / day multiple, ophthalmic Recommended Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9715679/	unhealthy, 62.1 years (range: 20-88 years) Health Status: unhealthy Age Group: 62.1 years (range: 20-88 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/9715679/
Ocular stinging	22%	1 drop 3 times / day multiple, ophthalmic Recommended Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9715679/	unhealthy, 62.1 years (range: 20-88 years) Health Status: unhealthy Age Group: 62.1 years (range: 20-88 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/9715679/
Headache	3%	1 drop 3 times / day multiple, ophthalmic Recommended Dose: 1 drop, 3 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9715679/	unhealthy, 62.1 years (range: 20-88 years) Health Status: unhealthy Age Group: 62.1 years (range: 20-88 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/9715679/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193		inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 1119

Drug as victim

Target	Modality	Activity
CYP2C19 1119	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2010/P201000028/63015300_22200AMX00308_A100_1.pdf#page=9 Page: (PMDA) 9	yes
CYP2C9 1193	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2010/P201000028/63015300_22200AMX00308_A100_1.pdf#page=9 Page: (PMDA) 9	yes
CYP3A4 1946	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2010/P201000028/63015300_22200AMX00308_A100_1.pdf#page=9 Page: (PMDA) 9	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.scirp.org/html/4-9102442_80769.htm

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4702	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4702
eMolecules	3715878	https://www.emolecules.com/cgi-bin/more?vid=3715878
MolPort	MolPort-005-941-739	https://www.molport.com/shop/molecule-link/MolPort-005-941-739
ZINC	ZINC000001530621	http://zinc15.docking.org/substances/ZINC000001530621

PubMed

Title	Date	PubMed
[Clinical evaluation of isopropyl unoprostone (Rescula), in the adjunctive treatment of primary open angle glaucoma].	2001	11605578
Dorzolamide-induced immune thrombocytopenia: a case report and literature review.	2001 Apr	11316096
Comparison of the additive intraocular pressure-lowering effect of latanoprost and dorzolamide when added to timolol in patients with open-angle glaucoma or ocular hypertension: a randomized, open-label, multicenter study in Greece.	2001 Aug	11558817
Twenty-four hour intraocular pressure reduction with latanoprost compared with pilocarpine as third-line therapy in exfoliation glaucoma.	2001 Feb	11318297
Treatment of intraocular pressure elevation after photorefractive keratectomy.	2001 Jul	11489570
Allergic contact dermatitis due to dorzolamide eyedrops.	2001 Jul	11422277
Carbonic anhydrase inhibitors: 4-sulfamoyl-benzenecarboxamides and 4-chloro-3-sulfamoyl-benzenecarboxamides with strong topical antiglaucoma properties.	2001 Jul 9	11425561
Brimonidine (Alphagan): a clinical profile four years after launch.	2001 Jul-Sep	11592536
[Severe hyperglycemia caused by dorzolamide].	2001 Jun	11438863
Management of glaucoma in pregnancy and lactation.	2001 Mar-Apr	11274697
Effect of topical administration of 2% dorzlamide hydrochloride or 2% dorzlamide hydrochloride-0.5% timolol maleate on intraocular pressure in clinically normal horses.	2001 May	11341390
Retrobulbar blood flow in glaucoma patients with nocturnal over-dipping in systemic blood pressure.	2001 Nov	11704025
[Prevention of early postoperative increase in intraocular pressure after phacoemulsification. Comparison of different antiglaucoma drugs].	2001 Oct	11699314
[Innovative glaucoma therapy. Glaucoma therapy with topical carbonic anhydrase inhibitors].	2001 Oct	11699313
Allergic contact blepharoconjunctivitis from dorzolamide.	2001 Oct	11683843
Drug points. Exacerbation of angina associated with latanoprost.	2001 Oct 6	11588081
Late normalization of melanocytomalytic intraocular pressure elevation following excision of iris melanocytoma.	2001 Sep	11688673
Cutaneous drug reaction case reports: from the world literature.	2002	11978142
Clinical pharmacokinetics of dorzolamide.	2002	11929320
Effects of topical antiglaucoma eye drops on prostaglandin E(2)-induced aqueous flare elevation in pigmented rabbits.	2002 Apr	11923258
The effect of latanoprost on circadian intraocular pressure.	2002 Aug	12204704
Cost analysis of glaucoma medications: a 3-year review.	2002 Aug	12169974
Choroidal detachment induced by dorzolamide 20 years after cataract surgery.	2002 Dec	12446402
Gateways to clinical trials.	2002 Jul-Aug	12224444
[Comparison of latanoprost monotherapy with timolol-dorzolamide combination in patients with open-angle glaucoma or ocular hypertension].	2002 Jun	12223948
[Corneal descompensation in patients with endothelial compromise treated with topical dorzolamide].	2002 Mar	11967735
Primary glaucoma in Burmese cats.	2002 Nov	12465823
Acetazolamide: future perspective in topical glaucoma therapeutics.	2002 Nov 6	12429455
The European glaucoma prevention study design and baseline description of the participants.	2002 Sep	12208707
Latanoprost : an update of its use in glaucoma and ocular hypertension.	2003	12795627
Cost-minimisation study of dorzolamide versus brinzolamide in the treatment of ocular hypertension and primary open-angle glaucoma: in four European countries.	2003	12558470
Comparison of the efficacy of the fixed-combination timolol/dorzolamide versus concomitant administration of timolol and dorzolamide.	2003 Apr	12804053
The effect of latanoprost, brimonidine, and a fixed combination of timolol and dorzolamide on circadian intraocular pressure in patients with glaucoma or ocular hypertension.	2003 Apr	12695241
New topical drugs for open-angle glaucoma.	2003 Feb	12630335
Blockers of carbonic anhydrase can cause increase of retinal capillary diameter, decrease of extracellular and increase of intracellular pH in rat retinal organ culture.	2003 Feb	12605269
Readability of ocular medication inserts.	2003 Feb	12567112
Effects of commercial antiglaucoma drugs to glutamate-induced [Ca2+)]i increase in cultured neuroblastoma cells.	2003 Jun	12828839
The effect of topical glaucoma medications evaluated by perimetry.	2003 Jun	12770987
The effects of dorzolamide on choroidal and retinal perfusion in non-exudative age related macular degeneration.	2003 Jun	12770975
Effects of twice daily application of 2% dorzolamide on intraocular pressure in normal cats.	2003 Jun	12753617
Four years later: a clinical update on latanoprost.	2003 Mar	12696636
Dorzolamide/timolol combination versus concomitant administration of brimonidine and timolol: six-month comparison of efficacy and tolerability.	2003 Mar	12623832
Influence of dorzolamide on corneal endothelium.	2003 Mar-Apr	12738544
[Therapy of normal tension glaucoma: effect of brinzolamide on ocular haemodynamics].	2003 May	12766822
Short-term effect of dorzolamide hydrochloride on central corneal thickness in humans with cornea guttata.	2003 May	12742838
Unoprostone as adjunctive therapy to timolol: a double masked randomised study versus brimonidine and dorzolamide.	2003 May	12714402

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Intraocular Hypertension One drop in the affected eye(s) three times a day Usual Adult Dose for Glaucoma (Open Angle) One drop in the affected eye(s) three times a day Applies to the following strength(s): 2%

Route of Administration: Topical

In Vitro Use Guide

Dorzolamide hydrochloride is a potent inhibitor of human CA isoenzyme II, with an IC50 value of 0.18 nM in vitro. In contrast, its inhibitory activity against human CA isozyme I is much weaker (IC50 value of 600 nM).

Name

Type

Language

DORZOLAMIDE [MI]

Preferred Name

English

DORZOLAMIDE

Official Name

English

DORZOLAMIDE, TRANS-(-)-

Common Name

English

DORZOLAMIDE [VANDF]

Common Name

English

(4S,6S)-4-(ETHYLAMINO)-5,6-DIHYDRO-6-METHYL-4H-THIENO(2,3-B)THIOPYRAN-2-SULFONAMIDE 7,7-DIOXIDE

Systematic Name

English

Dorzolamide [WHO-DD]

Common Name

English

dorzolamide [INN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

S01EC03