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
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
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 Date1995 |
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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 Date1995 |
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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 Date1995 |
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 |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
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 |
---|---|---|
Attenuation of hydrochlorothiazide-induced hypokalemia in dogs by a beta-adrenergic blocking drug, timolol. | 1975 Jun-Jul |
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Amelioration of bendrofluazide-induced hypokalemia by timolol. | 1977 Jul |
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Randomised study of six beta-blockers and a thiazide diuretic in essential hypertension. | 1978 Aug 5 |
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Severe bradycardia due to interaction of timolol eye drops and verapamil. | 1987 Jan 17 |
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Topical beta-blocker therapy and central nervous system side effects. A preliminary study comparing betaxolol and timolol. | 1988 Jul |
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[Timolol ophthalmic solution and atrio-ventricular block syncope]. | 1989 Jan |
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[Timolol: adverse cardiorespiratory effects]. | 1989 May |
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[Raynaud syndrome following timolol-containing eyedrops]. | 1990 |
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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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The free amino acids and the aqueous humor pH after antiglaucomatics in vitro. | 2003 |
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Elevated intraocular pressure associated with steroid treatment for infantile spasms. | 2003 Apr |
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The efficacy and safety of brimonidine 0.2% compared with timolol 0.5% in glaucoma: a randomized clinical trial on Taiwanese patients. | 2003 May |
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Improvement of the ocular bioavailability of timolol by sorbic acid. | 2004 Mar 19 |
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Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma. | 2004 Sep |
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Polymorphism of the bm86 gene in South American strains of the cattle tick Boophilus microplus. | 2005 |
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[Complete atrioventricular block secondary to application of timolol eyedrops: importance of the preanesthetic interview]. | 2005 Aug-Sep |
|
The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. | 2005 Feb |
|
[Economic impact of eyedrop cost in glaucoma treatment]. | 2005 Jan-Feb |
|
Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
Three cases of Descemet's membrane detachment after cataract surgery. | 2005 Oct 31 |
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Postoperative IOP prophylaxis practice following uncomplicated cataract surgery: a UK-wide consultant survey. | 2005 Oct 7 |
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Setting priorities for environmental sanitation interventions based on epidemiological criteria: a Brazilian study. | 2005 Sep |
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Syncope and falls due to timolol eye drops. | 2006 Apr 22 |
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[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 |
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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 |
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Atishoo! Atishoo! we all fall down! | 2006 Jul |
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24-Hour control with a latanoprost-timolol fixed combination vs timolol alone. | 2006 Nov |
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Hypotony and choroidal detachment as a complication of topical combined timolol and dorzolamide. | 2007 Apr |
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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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Sinoatrial block induced by timolol eyedrops. | 2007 Feb |
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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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Effects of topical antiglaucoma medications on corneal epithelium as evaluated by gene expression patterns. | 2007 Oct |
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[Late postoperative choroidal detachment]. | 2008 |
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Efficacy and safety of latanoprost versus pilocarpine/timolol maleate fixed combination in patients with primary open-angle glaucoma or ocular hypertension. | 2008 Dec |
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Cost analysis of glaucoma medications. | 2008 Jan |
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Evaluation of aqueous humor concentrations of Istalol and Betimol following a single ocular instillation in rabbit eyes. | 2008 Oct |
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A case of melancholic depression induced by beta-blocker antiglaucoma agents. | 2008 Oct 6 |
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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 |
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Role of fixed-combination brinzolamide 1%/timolol 0.5% in the treatment of elevated intraocular pressure in open-angle glaucoma and ocular hypertension. | 2009 |
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Oral versus topical carbonic anhydrase inhibitors in ocular hypertension after scleral tunnel cataract surgery. | 2009 |
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Cytochrome oxidase 2D6 gene polymorphism in primary open-angle glaucoma with various effects to ophthalmic timolol. | 2009 Apr |
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Effect of latanoprost and timolol on the histopathology of the human conjunctiva. | 2009 Feb |
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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 |
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Effects of timolol-related ophthalmic solutions on cultured human conjunctival cells. | 2010 Nov |
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Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells. | 2010 Oct 21 |
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Factors which influenced the decentralisation of leprosy control activities in the municipality of Betim, Minas Gerais State, Brazil. | 2010 Sep |
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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
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Edited
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Record UNII |
5JKY92S7BR
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Record Status |
Validated (UNII)
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Record Version |
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C29576
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Related Record | Type | Details | ||
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TARGET -> AGONIST |
NON-SELECTIVE
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METABOLIC ENZYME -> SUBSTRATE | |||
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SOLVATE->ANHYDROUS |
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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SALT/SOLVATE -> PARENT |
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TARGET -> AGONIST |
NON-SELECTIVE
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SALT/SOLVATE -> PARENT |
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
MAJOR
URINE
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METABOLITE -> PARENT |
MAJOR
URINE
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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