Details of the Drug

General Information of Drug (ID: DMA17D0)

Drug Name

Dorzolamide

Synonyms

Trusopt; Dorzolamide (DZA); Dorzolamide (INN); Trusopt (TN); (4S,6S)-4-(ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide; (4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxo-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide; (4S,6S)-4-Ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda*6*-thieno[2,3-b]thiopyran-2-sulfonic acid amide; (4S,trans)-4-(ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide; (4S-TRANS)-4-(ETHYLAMINO)-5,6-DIHYDRO-6-METHYL-4H-THIENO(2,3-B)THIOPYRAN-2-SULFONAMIDE-7,7-DIOXIDE

Indication

Disease Entry	ICD 11	Status	REF
Ocular hypertension	9C61.01	Approved	[1]
Open-angle glaucoma	9C61	Approved	[2]
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Therapeutic Class

Antihypertensive Agents

Affected Organisms

Humans and other mammals

ATC Code

S01EC03: Dorzolamide

S01EC: Carbonic anhydrase inhibitors

S01E: ANTIGLAUCOMA PREPARATIONS AND MIOTICS

S01: OPHTHALMOLOGICALS

S: SENSORY ORGANS

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

324.4

Logarithm of the Partition Coefficient (xlogp)

0.4

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
Elimination: 10% of drug is excreted from urine in the unchanged form [3]
Half-life: The concentration or amount of drug in body reduced by one-half in more than 4 months [4]
Metabolism: The drug is metabolized via the liver [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.08221 micromolar/kg/day [5]
Water Solubility: The ability of drug to dissolve in water is measured as 3.9 mg/mL [3]

Chemical Identifiers

Formula: C10H16N2O4S3
IUPAC Name: (4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxo-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide
Canonical SMILES: CCN[C@H]1C[C@@H](S(=O)(=O)C2=C1C=C(S2)S(=O)(=O)N)C
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
InChIKey: IAVUPMFITXYVAF-XPUUQOCRSA-N

Cross-matching ID

PubChem CID: 5284549
ChEBI ID: CHEBI:4702
CAS Number: 120279-96-1
UNII: 9JDX055TW1
DrugBank ID: DB00869
TTD ID: D05UYW
INTEDE ID: DR0536

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Carbonic anhydrase II (CA-II)	TTANPDJ	CAH2_HUMAN	Inhibitor	[6]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[7]
Cytochrome P450 2E1 (CYP2E1)_{Main DME}	DEVDYN7	CP2E1_HUMAN	Substrate	[8]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Ocular hypertension

ICD Disease Classification

9C61.01

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Carbonic anhydrase II (CA-II)	DTT	CA2	7.95E-08	0.52	0.33
Cytochrome P450 2E1 (CYP2E1)	DME	CYP2E1	1.91E-13	6.46E-02	3.30E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	1.07E-11	-1.16E-01	-2.53E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.87E-03	-6.67E-02	-2.12E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dorzolamide (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Aspirin	DM672AH	Major	Increased plasma concentration of Dorzolamide and Aspirin due to competitive binding of plasma proteins.	Pain [MG30-MG3Z]	[9]
Choline salicylate	DM8P137	Major	Increased risk of metabolic acidosis by the combination of Dorzolamide and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[9]
Salsalate	DM13P4C	Major	Increased plasma concentration of Dorzolamide and Salsalate due to competitive binding of plasma proteins.	Rheumatoid arthritis [FA20]	[9]
Salicyclic acid	DM2F8XZ	Major	Increased risk of metabolic acidosis by the combination of Dorzolamide and Salicyclic acid.	Seborrhoeic dermatitis [EA81]	[9]
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References

1	Dorzolamide FDA Label
2	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6810).
3	BDDCS applied to over 900 drugs
4	FDA Approved Drug Products: TRUSOPT (dorzolamide hydrochloride) ophthalmic solution
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorg Med Chem. 2009 Jul 15;17(14):5054-8.
7	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
8	In vitro metabolism of dorzolamide, a novel potent carbonic anhydrase inhibitor, in rat liver microsomes. Drug Metab Dispos. 1994 Nov-Dec;22(6):916-21.
9	Cowan RA, Hartnell GG, Lowdell CP, Baird IM, Leak AM "Metabolic acidosis induced by carbonic anhydrase inhibitors and salicylates in patients with normal renal function." Br Med J (Clin Res Ed) 289 (1984): 347-8. [PMID: 6432091]