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Details

Stereochemistry ABSOLUTE
Molecular Formula C13H24N4O3S
Molecular Weight 316.4213
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIMOLOL ANHYDROUS

SMILES

CC(C)(C)NC[C@@]([H])(COc1c(nsn1)N2CCOCC2)O

InChI

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

HIDE SMILES / InChI

Molecular Formula C13H24N4O3S
Molecular Weight 316.4213
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
Attenuation of hydrochlorothiazide-induced hypokalemia in dogs by a beta-adrenergic blocking drug, timolol.
1975 Jun-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
Topical beta-blocker therapy and central nervous system side effects. A preliminary study comparing betaxolol and timolol.
1988 Jul
[Timolol: adverse cardiorespiratory effects].
1989 May
Depression associated with diltiazem.
1989 Sep 23
[Raynaud syndrome following timolol-containing eyedrops].
1990
Complete heart block after topical timolol.
1990 Aug
Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine.
1990 Sep
[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
Plasma timolol concentrations of timolol maleate: timolol gel-forming solution (TIMOPTIC-XE) once daily versus timolol maleate ophthalmic solution twice daily.
2001 Jul
[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
Comparison of aqueous and gellan ophthalmic timolol with placebo on the 24-hour heart rate response in patients on treatment for glaucoma.
2001 Nov
Timolol increased retrobulbar flow velocities in untreated glaucoma eyes but not in ocular hypertension.
2001 Oct
[The pH reaction in aqueous humor to antiglaucoma agents of various concentrations and pH levels].
2001 Sep
Third degree AC block due to ophthalmic timilol solution.
2001 Sep-Oct
[Physiologic significance of the interaction between timolol and free amino acids in eye structures].
2002 May
One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular hypertension.
2002 Oct
Soft contact lenses capable of sustained delivery of timolol.
2002 Oct
The free amino acids and the aqueous humor pH after antiglaucomatics in vitro.
2003
Medical therapy cost considerations for glaucoma.
2003 Jul
Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma.
2004 Sep
Reversal of laser in situ keratomileusis-induced ectasia with intraocular pressure reduction.
2005 Aug
[Complete atrioventricular block secondary to application of timolol eyedrops: importance of the preanesthetic interview].
2005 Aug-Sep
[Economic impact of eyedrop cost in glaucoma treatment].
2005 Jan-Feb
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
Setting priorities for environmental sanitation interventions based on epidemiological criteria: a Brazilian study.
2005 Sep
Syncope and falls due to timolol eye drops.
2006 Apr 22
[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
24-Hour control with a latanoprost-timolol fixed combination vs timolol alone.
2006 Nov
Hypotony and choroidal detachment as a complication of topical combined timolol and dorzolamide.
2007 Apr
[Effect of the mixture of timoptol and amino acid taurine in the bioregulation of the intraocular pressure in rabbits].
2007 Jul
[Late postoperative choroidal detachment].
2008
Recent advances in pharmacotherapy of glaucoma.
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
Role of fixed-combination brinzolamide 1%/timolol 0.5% in the treatment of elevated intraocular pressure in open-angle glaucoma and ocular hypertension.
2009
Oral versus topical carbonic anhydrase inhibitors in ocular hypertension after scleral tunnel cataract surgery.
2009
Cytochrome oxidase 2D6 gene polymorphism in primary open-angle glaucoma with various effects to ophthalmic timolol.
2009 Apr
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
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
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 Sat Jun 26 15:37:22 UTC 2021
Edited
by admin
on Sat Jun 26 15:37:22 UTC 2021
Record UNII
5JKY92S7BR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TIMOLOL ANHYDROUS
Common Name English
2-PROPANOL, 1-((1,1-DIMETHYLETHYL)AMINO)-3-((4-(4-MORPHOLINYL)-1,2,5-THIADIAZOL-3-YL)OXY)-, (S)-
Systematic Name English
TIMOLOL [INN]
Common Name English
TIMOLOL [WHO-DD]
Common Name English
TIMOLOL [HSDB]
Common Name English
TIMOLOL [MI]
Common Name English
2-PROPANOL, 1-((1,1-DIMETHYLETHYL)AMINO)-3-((4-(4-MORPHOLINYL)-1,2,5-THIADIAZOL-3-YL)OXY)-, (2S)-
Systematic Name English
(S)-1-(TERT-BUTYLAMINO)-3-((4-MORPHOLINO-1,2,5-THIADIAZOL-3-YL)OXY)-2-PROPANOL
Systematic Name English
Classification Tree Code System Code
NDF-RT N0000000161
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
WHO-ATC C07AA06
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
NDF-RT N0000175556
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
WHO-ATC S01ED01
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
NCI_THESAURUS C29576
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
Code System Code Type Description
FDA UNII
5JKY92S7BR
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY
EPA CompTox
26839-75-8
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY
INN
3415
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY
ECHA (EC/EINECS)
248-032-6
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY
MERCK INDEX
M10871
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C90802
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY
CAS
26839-75-8
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY
RXCUI
1546004
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY RxNorm
PUBCHEM
33624
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY
DRUG BANK
DB00373
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY
HSDB
6533
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY
EVMPD
SUB11069MIG
Created by admin on Sat Jun 26 15:37:23 UTC 2021 , Edited by admin on Sat Jun 26 15:37:23 UTC 2021
PRIMARY
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