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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

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
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
Complete heart block after topical timolol.
1990 Aug
[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
Nightmares with topical beta-blocker.
2000 Oct
[Change in the pH of aqueous humor after administration of anti-glaucoma agents in rabbits in vivo].
2001 Jul
Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure.
2001 May
Third degree AC block due to ophthalmic timilol solution.
2001 Sep-Oct
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
One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular hypertension.
2002 Oct
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
Medical therapy cost considerations for glaucoma.
2003 Jul
Antiglaucoma eye drop pulses--increased interleukin-6 secretion by Tenon's capsule fibroblast cultures.
2004 Jun
[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
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
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
[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
[Late postoperative choroidal detachment].
2008
Role of endogenous RGS proteins on endothelial ERK 1/2 activation.
2008 Dec
Optic atrophy, necrotizing anterior scleritis and keratitis presenting in association with Streptococcal Toxic Shock Syndrome: a case report.
2008 Feb 29
[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
Oral versus topical carbonic anhydrase inhibitors in ocular hypertension after scleral tunnel cataract surgery.
2009
Effect of latanoprost and timolol on the histopathology of the human conjunctiva.
2009 Feb
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 Wed Jul 05 23:56:30 UTC 2023
Edited
by admin
on Wed Jul 05 23:56:30 UTC 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 Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
WHO-ATC C07AA06
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
NDF-RT N0000175556
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
WHO-ATC S01ED01
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
NCI_THESAURUS C29576
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
Code System Code Type Description
FDA UNII
5JKY92S7BR
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY
EPA CompTox
DTXSID4023674
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY
INN
3415
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY
ECHA (EC/EINECS)
248-032-6
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY
MERCK INDEX
M10871
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY Merck Index
NCI_THESAURUS
C90802
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY
CAS
26839-75-8
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY
RXCUI
1546004
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY RxNorm
SMS_ID
100000089192
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY
PUBCHEM
33624
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY
DAILYMED
5JKY92S7BR
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY
DRUG BANK
DB00373
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY
HSDB
6533
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 2023
PRIMARY
EVMPD
SUB11069MIG
Created by admin on Wed Jul 05 23:56:31 UTC 2023 , Edited by admin on Wed Jul 05 23:56:31 UTC 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
Related Record Type Details
ACTIVE MOIETY