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
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
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 |
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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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Regulation of diamine oxidase expression by beta 2-adrenoceptors in normal and hypertrophic rat kidney. | 1985 Jun 30 |
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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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Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine. | 1990 Sep |
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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 |
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One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular hypertension. | 2002 Oct |
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Soft contact lenses capable of sustained delivery of timolol. | 2002 Oct |
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Readability of ocular medication inserts. | 2003 Feb |
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Medical therapy cost considerations for glaucoma. | 2003 Jul |
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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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[A combination of timoptol and L-arginine HCl: a regulator of intraocular pressure in rabbits]. | 2003 Sep |
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Antiglaucoma eye drop pulses--increased interleukin-6 secretion by Tenon's capsule fibroblast cultures. | 2004 Jun |
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A case of clarithromycin-induced manic episode (antibiomania). | 2004 Mar |
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Improvement of the ocular bioavailability of timolol by sorbic acid. | 2004 Mar 19 |
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[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 |
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Binding of (-)-[3H]-CGP12177 at two sites in recombinant human beta 1-adrenoceptors and interaction with beta-blockers. | 2004 May |
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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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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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The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. | 2005 Feb |
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[Economic impact of eyedrop cost in glaucoma treatment]. | 2005 Jan-Feb |
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Factors associated with readmission to a general hospital in Brazil. | 2005 Jul-Aug |
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Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
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[The rabbit IOP and pupil values after application of aminoacid L-lysine and antiglaucomatic Timoptol mixture]. | 2005 Mar |
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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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Types of Glaucoma and recent trends applied in treatment: Observations from a Glaucoma Training Workshop in the Gambia. | 2005 Sep |
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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 |
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[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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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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[Late postoperative choroidal detachment]. | 2008 |
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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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Cost analysis of glaucoma medications. | 2008 Jan |
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[Influence on tear film after instillation of timolol maleate ophthalmic gel-forming solution examination by a tear film stability analysis system]. | 2008 Jun |
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Recent advances in pharmacotherapy of glaucoma. | 2008 Oct |
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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 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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Cytochrome P450 2D6 enzyme neuroprotects against 1-methyl-4-phenylpyridinium toxicity in SH-SY5Y neuronal cells. | 2010 Apr |
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.
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S01ED01
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QS01ED01
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21.4
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C07AA06
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QC07AA06
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LIVERTOX |
NBK548254
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NCI_THESAURUS |
C29576
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QC07BA06
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91524-16-2
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DB00373
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TIMOLOL
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100000087971
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Timolol
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CHEMBL499
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565
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D013999
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ACTIVE MOIETY
SUBSTANCE RECORD