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
Effects of commercial antiglaucoma drugs to glutamate-induced [Ca2+)]i increase in cultured neuroblastoma cells.	2003-06	12828839
The effect of topical glaucoma medications evaluated by perimetry.	2003-06	12770987
The effects of dorzolamide on choroidal and retinal perfusion in non-exudative age related macular degeneration.	2003-06	12770975
Effects of twice daily application of 2% dorzolamide on intraocular pressure in normal cats.	2003-06	12753617
Carbonic anhydrase inhibitors. Inhibition of tumor-associated isozyme IX by halogenosulfanilamide and halogenophenylaminobenzolamide derivatives.	2003-05-22	12747790
Influence of dorzolamide on corneal endothelium.	2003-05-10	12738544
[Therapy of normal tension glaucoma: effect of brinzolamide on ocular haemodynamics].	2003-05	12766822
Short-term effect of dorzolamide hydrochloride on central corneal thickness in humans with cornea guttata.	2003-05	12742838
Unoprostone as adjunctive therapy to timolol: a double masked randomised study versus brimonidine and dorzolamide.	2003-05	12714402
Comparison of the efficacy of the fixed-combination timolol/dorzolamide versus concomitant administration of timolol and dorzolamide.	2003-04	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.	2003-04	12695241
Acute and chronic ocular symptoms of dorzolamide 2% compared with placebo.	2003-04	12671470
Carbonic anhydrase inhibitors: inhibition of the tumor-associated isozyme IX with aromatic and heterocyclic sulfonamides.	2003-03-24	12643899
Comparative analysis of the effects of dorzolamide and latanoprost on ocular hemodynamics in normal tension glaucoma patients.	2003-03-15	12635671
Four years later: a clinical update on latanoprost.	2003-03	12696636
Dorzolamide/timolol combination versus concomitant administration of brimonidine and timolol: six-month comparison of efficacy and tolerability.	2003-03	12623832
[Glaucoma: an ocular blood flow disorder?].	2003-02	12650170
New topical drugs for open-angle glaucoma.	2003-02	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.	2003-02	12605269
Readability of ocular medication inserts.	2003-02	12567112
Timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and unoprostone 0.15% given twice daily to patients with primary open-angle glaucoma or ocular hypertension.	2003-02	12566015
The efficacy and safety of the timolol/dorzolamide fixed combination vs latanoprost in exfoliation glaucoma.	2003-01	12579169
Latanoprost : an update of its use in glaucoma and ocular hypertension.	2003	12795627
Experience with COSOPT, the fixed combination of timolol and dorzolamide, gained in Swiss ophthalmologists' offices.	2003	12740152
Cost-minimisation study of dorzolamide versus brinzolamide in the treatment of ocular hypertension and primary open-angle glaucoma: in four European countries.	2003	12558470
Evaluation of the intraocular pressure-reducing effect of latanoprost as monotherapy in open-angle glaucoma.	2002-12	12528287
A comparison of the effects on intraocular pressure of latanoprost 0.005% and the fixed combination of dorzolamide 2% and timolol 0.5% in patients with open-angle glaucoma.	2002-12	12485286
The short-term IOP-lowering effect of brimonidine 0.2% and dorzolomide 2% combination in primary open-angle glaucoma.	2002-12	12485285
An update on bimatoprost in glaucoma therapy.	2002-12	12472372
Choroidal detachment induced by dorzolamide 20 years after cataract surgery.	2002-12	12446402
Acetazolamide: future perspective in topical glaucoma therapeutics.	2002-11-06	12429455
Functional analysis of retinal vessel diameter reaction to artificially raised intraocular pressure in glaucoma patients with and without dorzolamide therapy.	2002-11	12510546
Primary glaucoma in Burmese cats.	2002-11	12465823
Dorzolamide X apraclonidine in the prevention of the intraocular pressure spike after Nd : YAG laser posterior capsulotomy.	2002-10	12658557
Inhibition of carbonic anhydrase activity in cultured bovine corneal endothelial cells by dorzolamide.	2002-10	12356834
Gateways to clinical trials.	2002-09-13	12224444
Reappraising first-line treatment in glaucoma management.	2002-09	12357857
Effects of anti-glaucoma medications on ganglion cell survival: the DBA/2J mouse model.	2002-09	12350421
The European glaucoma prevention study design and baseline description of the participants.	2002-09	12208707
Latanoprost versus combined timolol and dorzolamide.	2002-08	12204712
The effect of latanoprost on circadian intraocular pressure.	2002-08	12204704
Cost analysis of glaucoma medications: a 3-year review.	2002-08	12169974
[Weill-Marchesani syndrome. Late athalamia following antiglaucomatous surgery].	2002-07	12098811
[Comparison of latanoprost monotherapy with timolol-dorzolamide combination in patients with open-angle glaucoma or ocular hypertension].	2002-06	12223948
Tolerability and efficacy of dorzolamide versus acetazolamide added to timolol.	2002-06	12099542
Inhibitors of NHE-1 Na+/H+ exchange reduce mouse intraocular pressure.	2002-06	12036996
The pulsatile ocular blood flow behaviour in open angle glaucoma patients after replacing timolol therapy with timolol and dorzolamide fixed combination: preliminary study.	2002	12390145
Comparison of latanoprost, brimonidine and a fixed combination of timolol and dorzolamide on circadian intraocular pressure in patients with primary open-angle glaucoma and ocular hypertension.	2002	12390144
Effect of brimonidine on patients undergoing uncontrolled IOP with beta-blockers.	2002	12390143
Choroidal effusion and shallowing of the anterior chamber after adjunctive therapy with latanoprost in a trabeculectomized patient with angle closure glaucoma.	2001	12498508

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