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Details

Stereochemistry ABSOLUTE
Molecular Formula C13H24N4O3S
Molecular Weight 316.42
Optical Activity ( - )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIMOLOL ANHYDROUS

SMILES

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

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 316.42
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

1995
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

1995
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

1995
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
[Timolol ophthalmic solution and atrio-ventricular block syncope].
1989 Jan
[Timolol: adverse cardiorespiratory effects].
1989 May
[Raynaud syndrome following timolol-containing eyedrops].
1990
Apraclonidine hydrochloride: an evaluation of plasma concentrations, and a comparison of its intraocular pressure lowering and cardiovascular effects to timolol maleate.
1990
Complete heart block after topical timolol.
1990 Aug
Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine.
1990 Sep
Polymorphism of the bm86 gene in South American strains of the cattle tick Boophilus microplus.
2005
On call. The top of my tongue has taken on a dark brown color and a fuzzy look. I don't have a sore throat and I can taste everything, but I'm a bit worried. I am 67, and my only medications are Timoptic and Xalatan-drops for glaucoma. Can you tell me what's wrong and what to do about it?
2005 Apr
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
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
Setting priorities for environmental sanitation interventions based on epidemiological criteria: a Brazilian study.
2005 Sep
Types of Glaucoma and recent trends applied in treatment: Observations from a Glaucoma Training Workshop in the Gambia.
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
Prospective comparative switch study from timolol 0.5% and latanoprost 0.005% to bimatoprost 0.03%.
2006 Jan-Feb
[The effect of glycine with timoptol on the rabbit IOP physiological values].
2006 Jul
Atishoo! Atishoo! we all fall down!
2006 Jul
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
Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on circadian intraocular pressure.
2007 Dec
Sinoatrial block induced by timolol eyedrops.
2007 Feb
[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
A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling.
2007 Oct 16
[Late postoperative choroidal detachment].
2008
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
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
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
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
Effect of latanoprost and timolol on the histopathology of the human conjunctiva.
2009 Feb
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
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
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 Fri Dec 15 16:30:40 GMT 2023
Edited
by admin
on Fri Dec 15 16:30:40 GMT 2023
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 [HSDB]
Common Name English
Timolol [WHO-DD]
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 Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
WHO-ATC C07AA06
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
NDF-RT N0000175556
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
WHO-ATC S01ED01
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
NCI_THESAURUS C29576
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
Code System Code Type Description
FDA UNII
5JKY92S7BR
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
EPA CompTox
DTXSID4023674
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
INN
3415
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
ECHA (EC/EINECS)
248-032-6
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
MERCK INDEX
m10871
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY Merck Index
NCI_THESAURUS
C90802
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
CAS
26839-75-8
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
RXCUI
1546004
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY RxNorm
SMS_ID
100000089192
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
PUBCHEM
33624
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
DAILYMED
5JKY92S7BR
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
DRUG BANK
DB00373
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
HSDB
6533
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
EVMPD
SUB11069MIG
Created by admin on Fri Dec 15 16:30:40 GMT 2023 , Edited by admin on Fri Dec 15 16:30:40 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> AGONIST
NON-SELECTIVE
METABOLIC ENZYME -> SUBSTRATE
SOLVATE->ANHYDROUS
METABOLIC ENZYME -> SUBSTRATE
MAJOR
SALT/SOLVATE -> PARENT
TARGET -> AGONIST
NON-SELECTIVE
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE -> PARENT
MAJOR
URINE
METABOLITE -> PARENT
MAJOR
URINE
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ACTIVE MOIETY