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Details

Stereochemistry ABSOLUTE
Molecular Formula C13H24N4O3S.C4H4O4
Molecular Weight 432.492
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of TIMOLOL MALEATE

SMILES

OC(=O)\C=C/C(O)=O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N2CCOCC2

InChI

InChIKey=WLRMANUAADYWEA-NWASOUNVSA-N
InChI=1S/C13H24N4O3S.C4H4O4/c1-13(2,3)14-8-10(18)9-20-12-11(15-21-16-12)17-4-6-19-7-5-17;5-3(6)1-2-4(7)8/h10,14,18H,4-9H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t10-;/m0./s1

HIDE SMILES / InChI

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Molecular Formula C13H24N4O3S
Molecular Weight 316.42
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Timolol is the non-selective Beta antagonist used as eye drops to treat increased pressure inside the eye such as in ocular hypertension and glaucoma. Timolol is also used for high blood pressure, chest pain due to insufficient blood flow to the heart, to prevent further complications after a heart attack, and to prevent migraines. Timolol is a beta1 and beta2 (non-selective) adrenergic receptor antagonist that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. Timolol, when applied topically on the eye, has the action of reducing elevated, as well as normal intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss and optic nerve damage. The precise mechanism of the ocular hypotensive action of Timolol is not clearly established at this time. Tonography and fluorophotometry studies of the timolol maleate ophthalmic solution in man suggest that its predominant action may be related to the reduced aqueous formation. However, in some studies, a slight increase in outflow facility was also observed. In a study of plasma drug concentration in six subjects, the systemic exposure to timolol was determined following once daily administration of Timolol Maleate Ophthalmic Gel Forming Solution 0.5% in the morning. The mean peak plasma concentration following this morning dose was 0.28 ng/mL. Side effects, when given in the eye, include burning sensation, eye redness, superficial punctate keratopathy, corneal numbness.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Attenuation of hydrochlorothiazide-induced hypokalemia in dogs by a beta-adrenergic blocking drug, timolol.
1975 Jun-Jul
Amelioration of bendrofluazide-induced hypokalemia by timolol.
1977 Jul
Randomised study of six beta-blockers and a thiazide diuretic in essential hypertension.
1978 Aug 5
Regulation of diamine oxidase expression by beta 2-adrenoceptors in normal and hypertrophic rat kidney.
1985 Jun 30
Severe bradycardia due to interaction of timolol eye drops and verapamil.
1987 Jan 17
Topical beta-blocker therapy and central nervous system side effects. A preliminary study comparing betaxolol and timolol.
1988 Jul
[Timolol ophthalmic solution and atrio-ventricular block syncope].
1989 Jan
[Timolol: adverse cardiorespiratory effects].
1989 May
Depression associated with diltiazem.
1989 Sep 23
[Raynaud syndrome following timolol-containing eyedrops].
1990
[Bradyarrhythmias secondary to the use of ophthalmic timolol. A report of 3 cases].
1992 Jan
Changes in depressive status associated with topical beta-blockers.
1992 Sep
[Bradycardia of an elderly patient caused by Timolol therapy in ocular hypertension].
1996
[Atrioventricular block secondary to topical ophthalmic beta blockers].
1999 Jul
A randomized, comparative open-label study on the efficacy of latanoprost and timolol in steroid induced ocular hypertension after photorefractive keratectomy.
2000 Jul-Sep
Nightmares with topical beta-blocker.
2000 Oct
[A comparative study of the ocular tolerance of 3 timolol-based preparations: the influence of preservatives on ocular tolerance].
2001 Jan
[Change in the pH of aqueous humor after administration of anti-glaucoma agents in rabbits in vivo].
2001 Jul
Comparison of the ocular hypotensive lipid AGN 192024 with timolol: dosing, efficacy, and safety evaluation of a novel compound for glaucoma management.
2001 Jul
Assessment of systemic adverse reactions induced by ophthalmic beta-adrenergic receptor antagonists.
2001 Jun
Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure.
2001 May
Timolol increased retrobulbar flow velocities in untreated glaucoma eyes but not in ocular hypertension.
2001 Oct
[A combination of timoptol and L-arginine HCl: a regulator of intraocular pressure in rabbits].
2003 Sep
[Effect of various anti-glaucoma eyedrops on human corneal epithelial cells].
2004 Feb
Antiglaucoma eye drop pulses--increased interleukin-6 secretion by Tenon's capsule fibroblast cultures.
2004 Jun
Improvement of the ocular bioavailability of timolol by sorbic acid.
2004 Mar 19
[Comparison of the effectiveness of a mixture of 10% L-arginine and HCl combined with 0.5% Timoptol and with 2% Trusopt: and the individual components on intraocular pressure in an experiment on rabbits].
2004 May
Binding of (-)-[3H]-CGP12177 at two sites in recombinant human beta 1-adrenoceptors and interaction with beta-blockers.
2004 May
Polymorphism of the bm86 gene in South American strains of the cattle tick Boophilus microplus.
2005
Alphagan allergy may increase the propensity for multiple eye-drop allergy.
2005 Feb
[Economic impact of eyedrop cost in glaucoma treatment].
2005 Jan-Feb
Factors associated with readmission to a general hospital in Brazil.
2005 Jul-Aug
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Three cases of Descemet's membrane detachment after cataract surgery.
2005 Oct 31
Types of Glaucoma and recent trends applied in treatment: Observations from a Glaucoma Training Workshop in the Gambia.
2005 Sep
[Effect of the mixture of timoptol and amino acid taurine in the bioregulation of the intraocular pressure in rabbits].
2007 Jul
Effects of topical antiglaucoma medications on corneal epithelium as evaluated by gene expression patterns.
2007 Oct
Efficacy and safety of latanoprost versus pilocarpine/timolol maleate fixed combination in patients with primary open-angle glaucoma or ocular hypertension.
2008 Dec
Optic atrophy, necrotizing anterior scleritis and keratitis presenting in association with Streptococcal Toxic Shock Syndrome: a case report.
2008 Feb 29
Comparison of the 24-hour intraocular pressure-lowering effects of latanoprost and dorzolamide/timolol fixed combination after 2 and 6 months of treatment.
2008 Jan
Cost analysis of glaucoma medications.
2008 Jan
[Influence on tear film after instillation of timolol maleate ophthalmic gel-forming solution examination by a tear film stability analysis system].
2008 Jun
Evaluation of aqueous humor concentrations of Istalol and Betimol following a single ocular instillation in rabbit eyes.
2008 Oct
Cytochrome oxidase 2D6 gene polymorphism in primary open-angle glaucoma with various effects to ophthalmic timolol.
2009 Apr
Effect of latanoprost and timolol on the histopathology of the human conjunctiva.
2009 Feb
Effects of timolol-related ophthalmic solutions on cultured human conjunctival cells.
2010 Nov
Factors which influenced the decentralisation of leprosy control activities in the municipality of Betim, Minas Gerais State, Brazil.
2010 Sep
Patents

Sample Use Guides

In Vivo Use Guide
Timolol Maleate Ophthalmic Gel Forming Solution is available in concentrations of 0.25% and 0.5%. The dose is one drop of Timolol Maleate Ophthalmic Gel Forming Solution (either 0.25% or 0.5%) in the affected eye(s) once a day.
Route of Administration: Topical
In Vitro Use Guide
Immortalized human meibomian gland epithelial cells (HMGECs) (n = 2-3 wells/treatment/experiment) were cultured with multiple concentrations of pilocarpine or timolol for up to 7 days. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract) and differentiation (azithromycin). Cells were enumerated using a hemocytometer and evaluated for morphology, neutral lipid staining, and lysosome accumulation. Timolol cause a dose-dependent decrease in the survival of IHMGECs.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:02:00 UTC 2019
Edited
by admin
on Mon Oct 21 20:02:00 UTC 2019
Record UNII
P8Y54F701R
Record Status Validated (UNII)
Record Version
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Name Type Language
TIMOLOL MALEATE
EP   MART.   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
USAN  
Official Name English
TIMOLOL MALEATE COMPONENT OF COMBIGAN
Common Name English
TIMOPTIC
Brand Name English
DUOTRAV COMPONENT TIMOLOL MALEATE
Brand Name English
(-)-1-(TERT-BUTYLAMINO)-3-((4-MORPHOLINO-1,2,5-THIADIAZOL-3-YL)OXY)-2-PROPANOL MALEATE (1:1) (SALT)
Common Name English
2-PROPANOL, 1-((1,1-DIMETHYLETHYL)AMINO)-3-((4-(4-MORPHOLINYL)-1,2,5-THIADIAZOL-3-YL)OXY)-, (S)-, (Z)-2-BUTENEDIOATE (1:1) (SALT)
Common Name English
TIMOLOL MALEATE COMPONENT OF DUOTRAV
Brand Name English
COSOPT COMPONENT TIMOLOL MALEATE
Common Name English
TIMOLOL MALEATE, S-ENANTIOMER
WHO-DD  
Common Name English
TIMOLOL MALEATE [USP]
Common Name English
TIMOLOL HYDROGEN MALEATE SALT
MI  
Common Name English
TIMOLOL MALEATE [USP-RS]
Common Name English
WP-934
Code English
TIMOLOL (AS MALEATE)
Common Name English
TIMOLOL MALEATE COMPONENT OF COSOPT
Common Name English
TIMOLOL MALEATE [ORANGE BOOK]
Common Name English
GANFORT COMPONENT TIMOLOL MALEATE
Brand Name English
XALACOM COMPONENT TIMOLOL MALEATE
Brand Name English
TIMOLOL MALEATE [WHO-DD]
Common Name English
COMBIGAN COMPONENT TIMOLOL MALEATE
Common Name English
ISTALOL
Brand Name English
AQUANIL
Common Name English
TIMOLOL MALEATE COMPONENT OF GANFORT
Brand Name English
TIMOLOL MALEATE [MART.]
Common Name English
TIMOLOL MALEATE [EP]
Common Name English
TIMOLOL MALEATE [WHO-IP]
Common Name English
TIMOLOL MALEATE SALT
Common Name English
OPHTAMOLOL
Common Name English
BLOCADREN
Brand Name English
TIMOLOL MALEATE [USAN]
Common Name English
TIMOLOLI MALEAS [WHO-IP LATIN]
Common Name English
TIMOLOL MALEATE, S-ENANTIOMER [WHO-DD]
Common Name English
TIMOLOL HYDROGEN MALEATE SALT [MI]
Common Name English
TIMOLOL MALEATE [VANDF]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS DUOTRAV (AUTHORIZED: OCULAR HYPERTENSION)
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
NCI_THESAURUS C29576
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
EMA ASSESSMENT REPORTS GANFORT (AUTHORIZED: OCULAR HYPERTENSION)
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
EMA ASSESSMENT REPORTS AZARGA (AUTHORIZED: GLAUCOMA, OPEN-ANGLE)
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
EMA ASSESSMENT REPORTS GANFORT (AUTHORIZED: GLAUCOMA, OPEN-ANGLE)
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
EMA ASSESSMENT REPORTS DUOTRAV (AUTHORIZED: GLAUCOMA, OPEN-ANGLE)
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
Code System Code Type Description
EVMPD
SUB04877MIG
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
PRIMARY
NCI_THESAURUS
C29501
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
PRIMARY
EVMPD
SUB04875MIG
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
PRIMARY
EPA CompTox
26921-17-5
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
PRIMARY
ChEMBL
CHEMBL499
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
PRIMARY
MERCK INDEX
M10871
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
PRIMARY Merck Index
RXCUI
42933
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
PRIMARY RxNorm
ECHA (EC/EINECS)
248-111-5
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
PRIMARY
CAS
26921-17-5
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
PRIMARY
PUBCHEM
5281056
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
TIMOLOL MALEATE
Created by admin on Mon Oct 21 20:02:00 UTC 2019 , Edited by admin on Mon Oct 21 20:02:00 UTC 2019
PRIMARY Description: A white or almost white powder; odourless or almost odourless. Solubility: Soluble in water, methanol R, and ethanol (~750 g/l) TS; practically insoluble in ether R. Category: Antiglaucoma drug. Storage: Timolol maleate should be kept in a well-closed container, protected from light. Requirement: Timolol maleate contains not less than 98.0% and not more than the equivalent of 101.0% of C13H24N4O3S,C4H4O4, calculated with reference to the dried substance.
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
USP
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
Related Record Type Details
IMPURITY -> PARENT
not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (GC)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
not more than the area of the principal peak in the chromatogram obtained with reference solution (d)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY