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 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 |
---|---|---|---|
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 |
---|---|---|
Amelioration of bendrofluazide-induced hypokalemia by timolol. | 1977 Jul |
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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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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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Complete heart block after topical timolol. | 1990 Aug |
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[Bradyarrhythmias secondary to the use of ophthalmic timolol. A report of 3 cases]. | 1992 Jan |
|
Changes in depressive status associated with topical beta-blockers. | 1992 Sep |
|
Nightmares with topical beta-blocker. | 2000 Oct |
|
[Change in the pH of aqueous humor after administration of anti-glaucoma agents in rabbits in vivo]. | 2001 Jul |
|
Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure. | 2001 May |
|
Third degree AC block due to ophthalmic timilol solution. | 2001 Sep-Oct |
|
Comparison of the affinity of beta-blockers for two states of the beta 1-adrenoceptor in ferret ventricular myocardium. | 2002 Jan |
|
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 |
|
One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular hypertension. | 2002 Oct |
|
Elevated intraocular pressure associated with steroid treatment for infantile spasms. | 2003 Apr |
|
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 |
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Medical therapy cost considerations for glaucoma. | 2003 Jul |
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Antiglaucoma eye drop pulses--increased interleukin-6 secretion by Tenon's capsule fibroblast cultures. | 2004 Jun |
|
[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 |
|
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 |
|
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 |
|
[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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Role of endogenous RGS proteins on endothelial ERK 1/2 activation. | 2008 Dec |
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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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[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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A case of melancholic depression induced by beta-blocker antiglaucoma agents. | 2008 Oct 6 |
|
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 |
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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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