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Details

Stereochemistry ABSOLUTE
Molecular Formula 2C13H24N4O3S.H2O
Molecular Weight 650.855
Optical Activity ( - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIMOLOL

SMILES

O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N2CCOCC2.CC(C)(C)NC[C@H](O)COC3=NSN=C3N4CCOCC4

InChI

InChIKey=TWBNMYSKRDRHAT-RCWTXCDDSA-N
InChI=1S/2C13H24N4O3S.H2O/c2*1-13(2,3)14-8-10(18)9-20-12-11(15-21-16-12)17-4-6-19-7-5-17;/h2*10,14,18H,4-9H2,1-3H3;1H2/t2*10-;/m00./s1

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C13H24N4O3S
Molecular Weight 316.42
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including https://www.drugs.com/cdi/timolol-drops.html | https://www.drugbank.ca/drugs/DB00373 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021398s007lbl.pdf | https://www.drugs.com/pro/timolol-gfs.html

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.2 nM [Kd]
7.9 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
BETIMOL

Approved Use

Betimol® is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

Launch Date

7.9660797E11
Primary
BETIMOL

Approved Use

Betimol® is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

Launch Date

7.9660797E11
Primary
BETIMOL

Approved Use

Betimol® is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

Launch Date

7.9660797E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
26 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIMOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
110 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIMOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.4 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIMOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1 drop 2 times / day steady, ophthalmic (starting)
Dose: 1 drop, 2 times / day
Route: ophthalmic
Route: steady
Dose: 1 drop, 2 times / day
Sources:
unhealthy
n = 8
Health Status: unhealthy
Condition: elevated intraocular pressure
Population Size: 8
Sources:
Other AEs: Stinging...
AEs

AEs

AESignificanceDosePopulation
Stinging 1 patient
1 drop 2 times / day steady, ophthalmic (starting)
Dose: 1 drop, 2 times / day
Route: ophthalmic
Route: steady
Dose: 1 drop, 2 times / day
Sources:
unhealthy
n = 8
Health Status: unhealthy
Condition: elevated intraocular pressure
Population Size: 8
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
likely
likely
Comment: potentiated systemic beta-blockade has been reported during combined treatment with quinidine and timolol, possibly because quinidine inhibits the metabolism of timolol via CYP2D6
Page: 7, 8, 19
PubMed

PubMed

TitleDatePubMed
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
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
[Raynaud syndrome following timolol-containing eyedrops].
1990
Complete heart block after topical timolol.
1990 Aug
[Atrioventricular block secondary to topical ophthalmic beta blockers].
1999 Jul
[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
Elevated intraocular pressure associated with steroid treatment for infantile spasms.
2003 Apr
The efficacy and safety of brimonidine 0.2% compared with timolol 0.5% in glaucoma: a randomized clinical trial on Taiwanese patients.
2003 May
[A combination of timoptol and L-arginine HCl: a regulator of intraocular pressure in rabbits].
2003 Sep
[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
Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma.
2004 Sep
Polymorphism of the bm86 gene in South American strains of the cattle tick Boophilus microplus.
2005
The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors.
2005 Feb
Alphagan allergy may increase the propensity for multiple eye-drop allergy.
2005 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
[The rabbit IOP and pupil values after application of aminoacid L-lysine and antiglaucomatic Timoptol mixture].
2005 Mar
Three cases of Descemet's membrane detachment after cataract surgery.
2005 Oct 31
Postoperative IOP prophylaxis practice following uncomplicated cataract surgery: a UK-wide consultant survey.
2005 Oct 7
[Reduction of the physiologic IOP value after instilation of the mixture of the 2 amino acid's (L-lysine and L-arginine) in timoptol--experiment on rabbit's].
2006 Jan
[Effect of the mixture of timoptol and amino acid taurine in the bioregulation of the intraocular pressure in rabbits].
2007 Jul
Role of endogenous RGS proteins on endothelial ERK 1/2 activation.
2008 Dec
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
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
Recent advances in pharmacotherapy of glaucoma.
2008 Oct
Evaluation of aqueous humor concentrations of Istalol and Betimol following a single ocular instillation in rabbit eyes.
2008 Oct
A case of melancholic depression induced by beta-blocker antiglaucoma agents.
2008 Oct 6
A patient preference comparison of Azarga (brinzolamide/timolol fixed combination) vs Cosopt (dorzolamide/timolol fixed combination) in patients with open-angle glaucoma or ocular hypertension.
2008 Sep
Short-term tolerability of once-daily timolol hemihydrate 0.5%, timolol maleate in sorbate 0.5%, and generic timolol maleate gel-forming solution 0.5% in glaucoma and/or ocular hypertension: a prospective, randomized, double-masked, active-controlled, three-period crossover pilot study.
2009 Oct
Cytochrome P450 2D6 enzyme neuroprotects against 1-methyl-4-phenylpyridinium toxicity in SH-SY5Y neuronal cells.
2010 Apr
Incidence, severity and factors related to drug-induced keratoepitheliopathy with glaucoma medications.
2010 Apr 26
Association of CYP2D6 single-nucleotide polymorphism with response to ophthalmic timolol in primary open-angle Glaucoma--a pilot study.
2010 Oct
Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells.
2010 Oct 21
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
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 Fri Dec 16 17:25:09 UTC 2022
Edited
by admin
on Fri Dec 16 17:25:09 UTC 2022
Record UNII
817W3C6175
Record Status Validated (UNII)
Record Version
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Name Type Language
TIMOLOL
EMA EPAR   ORANGE BOOK   USAN   VANDF  
USAN  
Official Name English
TIMOLOL [USAN]
Common Name English
TIMOLOL [ORANGE BOOK]
Common Name English
Timolol hemihydrate [WHO-DD]
Common Name English
(S)-1-(tert-Butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy]-2-propanol hemihydrate
Common Name English
TIMOLOL [EMA EPAR]
Common Name English
TIMOLOL HEMIHYDRATE [VANDF]
Common Name English
BETIMOL
Brand Name English
TIMOLOL HEMIHYDRATE
VANDF   WHO-DD  
Common Name English
2-PROPANOL, 1-((1,1-DIMETHYLETHYL)AMINO)-3-((4-(4-MORPHOLINYL)-1,2,5-THIADIAZOL-3-YL)OXY)-, HEMIHYDRATE, (S)-
Common Name English
TIMOLOL [VANDF]
Common Name English
Classification Tree Code System Code
WHO-ATC C07BA06
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
WHO-ATC C07DA06
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
WHO-ATC S01ED51
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
WHO-VATC QS01ED51
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
NDF-RT N0000175556
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
WHO-ATC S01ED01
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
WHO-VATC QS01ED01
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
WHO-ESSENTIAL MEDICINES LIST 21.4
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
WHO-ATC C07AA06
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
WHO-VATC QC07AA06
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
LIVERTOX NBK548254
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
NCI_THESAURUS C29576
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
WHO-VATC QC07BA06
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
Code System Code Type Description
CAS
91524-16-2
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
DRUG BANK
DB00373
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
WIKIPEDIA
TIMOLOL
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
RXCUI
10600
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
ALTERNATIVE
FDA UNII
817W3C6175
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
USAN
W-130
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
LACTMED
Timolol
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
ChEMBL
CHEMBL499
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
IUPHAR
565
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
CHEBI
60787
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
CHEBI
9599
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
EPA CompTox
DTXSID70238611
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
RXCUI
221172
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
NCI_THESAURUS
C47757
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
EVMPD
SUB22330
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
DRUG CENTRAL
4061
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
DAILYMED
817W3C6175
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
MESH
D013999
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
PUBCHEM
62933
Created by admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
PRIMARY
Related Record Type Details
ANHYDROUS->SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY