Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C13H24N4O3S.C4H4O4 |
Molecular Weight | 432.492 |
Optical Activity | ( - ) |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C/C(O)=O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N2CCOCC2
InChI
InChIKey=WLRMANUAADYWEA-NWASOUNVSA-N
InChI=1S/C13H24N4O3S.C4H4O4/c1-13(2,3)14-8-10(18)9-20-12-11(15-21-16-12)17-4-6-19-7-5-17;5-3(6)1-2-4(7)8/h10,14,18H,4-9H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t10-;/m0./s1
Molecular Formula | C4H4O4 |
Molecular Weight | 116.0722 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
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 |
DescriptionCurator'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
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.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2903243 |
0.2 nM [Kd] | ||
Target ID: CHEMBL213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2903243 |
7.9 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | BETIMOL Approved UseBetimol® is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Launch Date7.9660797E11 |
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Primary | BETIMOL Approved UseBetimol® is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Launch Date7.9660797E11 |
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Primary | BETIMOL Approved UseBetimol® is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Launch Date7.9660797E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
26 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18201139/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
110 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18201139/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18201139/ |
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
Dose | Population | Adverse 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... Other AEs: Stinging (1 patient) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
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OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
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Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021516s000_Istalol_BioPharmr.pdf Page: 5.0 |
likely | |||
Page: 7, 8, 19 |
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
Title | Date | PubMed |
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Randomised study of six beta-blockers and a thiazide diuretic in essential hypertension. | 1978 Aug 5 |
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[Timolol ophthalmic solution and atrio-ventricular block syncope]. | 1989 Jan |
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Apraclonidine hydrochloride: an evaluation of plasma concentrations, and a comparison of its intraocular pressure lowering and cardiovascular effects to timolol maleate. | 1990 |
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Complete heart block after topical timolol. | 1990 Aug |
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Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine. | 1990 Sep |
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Changes in depressive status associated with topical beta-blockers. | 1992 Sep |
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[Bradycardia of an elderly patient caused by Timolol therapy in ocular hypertension]. | 1996 |
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Beta-blocker eyedrops and nocturnal arterial hypotension. | 1999 Sep |
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Plasma timolol concentrations of timolol maleate: timolol gel-forming solution (TIMOPTIC-XE) once daily versus timolol maleate ophthalmic solution twice daily. | 2001 Jul |
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[Change in the pH of aqueous humor after administration of anti-glaucoma agents in rabbits in vivo]. | 2001 Jul |
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Assessment of systemic adverse reactions induced by ophthalmic beta-adrenergic receptor antagonists. | 2001 Jun |
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Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure. | 2001 May |
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Comparison of the affinity of beta-blockers for two states of the beta 1-adrenoceptor in ferret ventricular myocardium. | 2002 Jan |
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Soft contact lenses capable of sustained delivery of timolol. | 2002 Oct |
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Mass spectrometric study of the photooxidation of the ophthalmic drugs timolol and pindolol. | 2003 Aug |
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Comparison of efficacy and tolerability between two gel-forming timolol maleate ophthalmic solutions in patients with glaucoma or ocular hypertension. | 2003 Jan-Feb |
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[A combination of timoptol and L-arginine HCl: a regulator of intraocular pressure in rabbits]. | 2003 Sep |
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Improvement of the ocular bioavailability of timolol by sorbic acid. | 2004 Mar 19 |
|
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 |
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Reversal of laser in situ keratomileusis-induced ectasia with intraocular pressure reduction. | 2005 Aug |
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[Complete atrioventricular block secondary to application of timolol eyedrops: importance of the preanesthetic interview]. | 2005 Aug-Sep |
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[Economic impact of eyedrop cost in glaucoma treatment]. | 2005 Jan-Feb |
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Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
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Three cases of Descemet's membrane detachment after cataract surgery. | 2005 Oct 31 |
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[The effect of glycine with timoptol on the rabbit IOP physiological values]. | 2006 Jul |
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Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on circadian intraocular pressure. | 2007 Dec |
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[Effect of the mixture of timoptol and amino acid taurine in the bioregulation of the intraocular pressure in rabbits]. | 2007 Jul |
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Optic atrophy, necrotizing anterior scleritis and keratitis presenting in association with Streptococcal Toxic Shock Syndrome: a case report. | 2008 Feb 29 |
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Evaluation of aqueous humor concentrations of Istalol and Betimol following a single ocular instillation in rabbit eyes. | 2008 Oct |
|
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 |
|
Incidence, severity and factors related to drug-induced keratoepitheliopathy with glaucoma medications. | 2010 Apr 26 |
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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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/pro/timolol-gfs.html
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28476050
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
Edited
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on
Fri Dec 16 19:06:39 UTC 2022
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Record UNII |
P8Y54F701R
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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EMA ASSESSMENT REPORTS |
DUOTRAV (AUTHORIZED: OCULAR HYPERTENSION)
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NCI_THESAURUS |
C29576
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EMA ASSESSMENT REPORTS |
GANFORT (AUTHORIZED: OCULAR HYPERTENSION)
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EMA ASSESSMENT REPORTS |
AZARGA (AUTHORIZED: GLAUCOMA, OPEN-ANGLE)
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EMA ASSESSMENT REPORTS |
GANFORT (AUTHORIZED: GLAUCOMA, OPEN-ANGLE)
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EMA ASSESSMENT REPORTS |
DUOTRAV (AUTHORIZED: GLAUCOMA, OPEN-ANGLE)
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DTXSID3047504
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CHEMBL499
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DBSALT000989
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42933
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757351
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1667406
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TIMOLOL MALEATE
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PRIMARY | Description: A white or almost white powder; odourless or almost odourless. Solubility: Soluble in water, methanol R, and ethanol (~750 g/l) TS; practically insoluble in ether R. Category: Antiglaucoma drug. Storage: Timolol maleate should be kept in a well-closed container, protected from light. Requirement: Timolol maleate contains not less than 98.0% and not more than the equivalent of 101.0% of C13H24N4O3S,C4H4O4, calculated with reference to the dried substance. |
Related Record | Type | Details | ||
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PARENT -> SALT/SOLVATE | |||
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PARENT -> SALT/SOLVATE | |||
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (TITRATION)
USP
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (TITRATION)
EP
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
UNSPECIFIED
CHROMATOGRAPHIC PURITY (GC)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
not more than the area of the principal peak in the chromatogram obtained with reference solution (d)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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ACTIVE MOIETY |