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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
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
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
[Timolol ophthalmic solution and atrio-ventricular block syncope].
1989 Jan
[Timolol: adverse cardiorespiratory effects].
1989 May
Depression associated with diltiazem.
1989 Sep 23
[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
[Bradycardia of an elderly patient caused by Timolol therapy in ocular hypertension].
1996
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
Assessment of systemic adverse reactions induced by ophthalmic beta-adrenergic receptor antagonists.
2001 Jun
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
Third degree AC block due to ophthalmic timilol solution.
2001 Sep-Oct
One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular hypertension.
2002 Oct
Topical beta blockers and atrioventricular block in the elderly.
2002 Oct-Dec
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
Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma.
2004 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
[The rabbit IOP and pupil values after application of aminoacid L-lysine and antiglaucomatic Timoptol mixture].
2005 Mar
Types of Glaucoma and recent trends applied in treatment: Observations from a Glaucoma Training Workshop in the Gambia.
2005 Sep
[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
[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
Cost analysis of glaucoma medications.
2008 Jan
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
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
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
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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