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

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

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
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: adverse cardiorespiratory effects].
1989 May
Apraclonidine hydrochloride: an evaluation of plasma concentrations, and a comparison of its intraocular pressure lowering and cardiovascular effects to timolol maleate.
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
Comparison of aqueous and gellan ophthalmic timolol with placebo on the 24-hour heart rate response in patients on treatment for glaucoma.
2001 Nov
[The pH reaction in aqueous humor to antiglaucoma agents of various concentrations and pH levels].
2001 Sep
Symptomatic bradycardia secondary to interaction between topical timolol maleate, verapamil, and flecainide: a case report.
2002 Apr
Comparison of the affinity of beta-blockers for two states of the beta 1-adrenoceptor in ferret ventricular myocardium.
2002 Jan
Effects of L-NAME and timolol on aqueous IL-1beta, IL-6, IL-8, TNF-alpha and NO levels after Nd:YAG laser iridotomy in rabbits.
2002 Jul-Aug
[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
Topical beta blockers and atrioventricular block in the elderly.
2002 Oct-Dec
The free amino acids and the aqueous humor pH after antiglaucomatics in vitro.
2003
Elevated intraocular pressure associated with steroid treatment for infantile spasms.
2003 Apr
Mass spectrometric study of the photooxidation of the ophthalmic drugs timolol and pindolol.
2003 Aug
Readability of ocular medication inserts.
2003 Feb
Comparison of efficacy and tolerability between two gel-forming timolol maleate ophthalmic solutions in patients with glaucoma or ocular hypertension.
2003 Jan-Feb
[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
A case of clarithromycin-induced manic episode (antibiomania).
2004 Mar
[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
Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma.
2004 Sep
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
[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
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
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
Efficacy and safety of latanoprost versus pilocarpine/timolol maleate fixed combination in patients with primary open-angle glaucoma or ocular hypertension.
2008 Dec
[Influence on tear film after instillation of timolol maleate ophthalmic gel-forming solution examination by a tear film stability analysis system].
2008 Jun
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
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
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 15:33:08 GMT 2023
Edited
by admin
on Fri Dec 15 15:33:08 GMT 2023
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 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
WHO-ATC C07DA06
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
WHO-ATC S01ED51
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WHO-VATC QS01ED51
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NDF-RT N0000175556
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WHO-ATC S01ED01
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WHO-VATC QS01ED01
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
WHO-ESSENTIAL MEDICINES LIST 21.4
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
WHO-ATC C07AA06
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WHO-VATC QC07AA06
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LIVERTOX NBK548254
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NCI_THESAURUS C29576
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WHO-VATC QC07BA06
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
Code System Code Type Description
CAS
91524-16-2
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
PRIMARY
DRUG BANK
DB00373
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
PRIMARY
WIKIPEDIA
TIMOLOL
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
PRIMARY
RXCUI
10600
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
ALTERNATIVE
FDA UNII
817W3C6175
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
PRIMARY
USAN
W-130
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
PRIMARY
SMS_ID
100000087971
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
PRIMARY
LACTMED
Timolol
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
PRIMARY
ChEMBL
CHEMBL499
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PRIMARY
IUPHAR
565
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PRIMARY
CHEBI
60787
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PRIMARY
CHEBI
9599
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PRIMARY
EPA CompTox
DTXSID70238611
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PRIMARY
RXCUI
221172
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
PRIMARY
NCI_THESAURUS
C47757
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PRIMARY
EVMPD
SUB22330
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PRIMARY
DRUG CENTRAL
4061
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PRIMARY
DAILYMED
817W3C6175
Created by admin on Fri Dec 15 15:33:08 GMT 2023 , Edited by admin on Fri Dec 15 15:33:08 GMT 2023
PRIMARY
MESH
D013999
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PRIMARY
PUBCHEM
62933
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PRIMARY
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