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 |
---|---|---|
Apraclonidine hydrochloride: an evaluation of plasma concentrations, and a comparison of its intraocular pressure lowering and cardiovascular effects to timolol maleate. | 1990 |
|
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 |
|
[The pH reaction in aqueous humor to antiglaucoma agents of various concentrations and pH levels]. | 2001 Sep |
|
Third degree AC block due to ophthalmic timilol solution. | 2001 Sep-Oct |
|
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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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 |
|
[Physiologic significance of the interaction between timolol and free amino acids in eye structures]. | 2002 May |
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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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Topical beta blockers and atrioventricular block in the elderly. | 2002 Oct-Dec |
|
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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Readability of ocular medication inserts. | 2003 Feb |
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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 |
|
Medical therapy cost considerations for glaucoma. | 2003 Jul |
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[Effect of various anti-glaucoma eyedrops on human corneal epithelial cells]. | 2004 Feb |
|
[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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Reversal of laser in situ keratomileusis-induced ectasia with intraocular pressure reduction. | 2005 Aug |
|
Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
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Syncope and falls due to timolol eye drops. | 2006 Apr 22 |
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A case of melancholic depression induced by beta-blocker antiglaucoma agents. | 2008 Oct 6 |
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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 |
|
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 |
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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Record UNII |
5JKY92S7BR
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Record Status |
Validated (UNII)
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C07AA06
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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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