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 |
0.2 nM [Kd] | ||
Target ID: CHEMBL213 |
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 |
|---|---|---|---|---|
| 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 |
|---|---|---|
| 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 |
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| [Timolol ophthalmic solution and atrio-ventricular block syncope]. | 1989 Jan |
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| [Bradyarrhythmias secondary to the use of ophthalmic timolol. A report of 3 cases]. | 1992 Jan |
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| Changes in depressive status associated with topical beta-blockers. | 1992 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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| [The pH reaction in aqueous humor to antiglaucoma agents of various concentrations and pH levels]. | 2001 Sep |
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| Symptomatic bradycardia secondary to interaction between topical timolol maleate, verapamil, and flecainide: a case report. | 2002 Apr |
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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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| One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular hypertension. | 2002 Oct |
|
| Mass spectrometric study of the photooxidation of the ophthalmic drugs timolol and pindolol. | 2003 Aug |
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| Readability of ocular medication inserts. | 2003 Feb |
|
| 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 |
|
| [A combination of timoptol and L-arginine HCl: a regulator of intraocular pressure in rabbits]. | 2003 Sep |
|
| [Effect of various anti-glaucoma eyedrops on human corneal epithelial cells]. | 2004 Feb |
|
| Antiglaucoma eye drop pulses--increased interleukin-6 secretion by Tenon's capsule fibroblast cultures. | 2004 Jun |
|
| 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 |
|
| [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 |
|
| Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma. | 2004 Sep |
|
| Polymorphism of the bm86 gene in South American strains of the cattle tick Boophilus microplus. | 2005 |
|
| Reversal of laser in situ keratomileusis-induced ectasia with intraocular pressure reduction. | 2005 Aug |
|
| [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 |
|
| Alphagan allergy may increase the propensity for multiple eye-drop allergy. | 2005 Feb |
|
| [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 |
|
| Postoperative IOP prophylaxis practice following uncomplicated cataract surgery: a UK-wide consultant survey. | 2005 Oct 7 |
|
| Setting priorities for environmental sanitation interventions based on epidemiological criteria: a Brazilian study. | 2005 Sep |
|
| Types of Glaucoma and recent trends applied in treatment: Observations from a Glaucoma Training Workshop in the Gambia. | 2005 Sep |
|
| Syncope and falls due to timolol eye drops. | 2006 Apr 22 |
|
| [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 |
|
| Atishoo! Atishoo! we all fall down! | 2006 Jul |
|
| 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 |
|
| Comparison of the 24-hour intraocular pressure-lowering effects of latanoprost and dorzolamide/timolol fixed combination after 2 and 6 months of treatment. | 2008 Jan |
|
| Cost analysis of glaucoma medications. | 2008 Jan |
|
| Recent advances in pharmacotherapy of glaucoma. | 2008 Oct |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
Sample Use Guides
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
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on
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Fri Dec 15 16:03:39 GMT 2023
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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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SUB04877MIG
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P8Y54F701R
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C29501
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DTXSID3047504
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CHEMBL499
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P8Y54F701R
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100000090033
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m10871
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DBSALT000989
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42933
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757351
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248-111-5
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26921-17-5
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5281056
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9600
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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 |