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
Molecular Formula | H2O |
Molecular Weight | 18.0153 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
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 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 |
|||
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 |
|||
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 |
|
Randomised study of six beta-blockers and a thiazide diuretic in essential hypertension. | 1978 Aug 5 |
|
Severe bradycardia due to interaction of timolol eye drops and verapamil. | 1987 Jan 17 |
|
Topical beta-blocker therapy and central nervous system side effects. A preliminary study comparing betaxolol and timolol. | 1988 Jul |
|
[Timolol ophthalmic solution and atrio-ventricular block syncope]. | 1989 Jan |
|
[Raynaud syndrome following timolol-containing eyedrops]. | 1990 |
|
Complete heart block after topical timolol. | 1990 Aug |
|
[Atrioventricular block secondary to topical ophthalmic beta blockers]. | 1999 Jul |
|
[A comparative study of the ocular tolerance of 3 timolol-based preparations: the influence of preservatives on ocular tolerance]. | 2001 Jan |
|
[Change in the pH of aqueous humor after administration of anti-glaucoma agents in rabbits in vivo]. | 2001 Jul |
|
Comparison of the ocular hypotensive lipid AGN 192024 with timolol: dosing, efficacy, and safety evaluation of a novel compound for glaucoma management. | 2001 Jul |
|
Assessment of systemic adverse reactions induced by ophthalmic beta-adrenergic receptor antagonists. | 2001 Jun |
|
Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure. | 2001 May |
|
Elevated intraocular pressure associated with steroid treatment for infantile spasms. | 2003 Apr |
|
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 |
|
[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 |
|
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 |
|
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 |
|
Three cases of Descemet's membrane detachment after cataract surgery. | 2005 Oct 31 |
|
Postoperative IOP prophylaxis practice following uncomplicated cataract surgery: a UK-wide consultant survey. | 2005 Oct 7 |
|
[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 |
|
[Effect of the mixture of timoptol and amino acid taurine in the bioregulation of the intraocular pressure in rabbits]. | 2007 Jul |
|
Role of endogenous RGS proteins on endothelial ERK 1/2 activation. | 2008 Dec |
|
Efficacy and safety of latanoprost versus pilocarpine/timolol maleate fixed combination in patients with primary open-angle glaucoma or ocular hypertension. | 2008 Dec |
|
Optic atrophy, necrotizing anterior scleritis and keratitis presenting in association with Streptococcal Toxic Shock Syndrome: a case report. | 2008 Feb 29 |
|
Cost analysis of glaucoma medications. | 2008 Jan |
|
[Influence on tear film after instillation of timolol maleate ophthalmic gel-forming solution examination by a tear film stability analysis system]. | 2008 Jun |
|
Recent advances in pharmacotherapy of glaucoma. | 2008 Oct |
|
Evaluation of aqueous humor concentrations of Istalol and Betimol following a single ocular instillation in rabbit eyes. | 2008 Oct |
|
A case of melancholic depression induced by beta-blocker antiglaucoma agents. | 2008 Oct 6 |
|
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 |
|
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 |
|
Incidence, severity and factors related to drug-induced keratoepitheliopathy with glaucoma medications. | 2010 Apr 26 |
|
Association of CYP2D6 single-nucleotide polymorphism with response to ophthalmic timolol in primary open-angle Glaucoma--a pilot study. | 2010 Oct |
|
Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells. | 2010 Oct 21 |
|
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
by
admin
on
Edited
Fri Dec 16 17:25:09 UTC 2022
by
admin
on
Fri Dec 16 17:25:09 UTC 2022
|
Record UNII |
817W3C6175
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
WHO-ATC |
C07BA06
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
WHO-ATC |
C07DA06
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
WHO-ATC |
S01ED51
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
WHO-VATC |
QS01ED51
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
NDF-RT |
N0000175556
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
WHO-ATC |
S01ED01
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
WHO-VATC |
QS01ED01
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
WHO-ESSENTIAL MEDICINES LIST |
21.4
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
WHO-ATC |
C07AA06
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
WHO-VATC |
QC07AA06
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
LIVERTOX |
NBK548254
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
NCI_THESAURUS |
C29576
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
||
|
WHO-VATC |
QC07BA06
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
91524-16-2
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
DB00373
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
TIMOLOL
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
10600
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
ALTERNATIVE | |||
|
817W3C6175
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
W-130
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
Timolol
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
CHEMBL499
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
565
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
60787
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
9599
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
DTXSID70238611
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
221172
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
C47757
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
SUB22330
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
4061
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
817W3C6175
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
D013999
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY | |||
|
62933
Created by
admin on Fri Dec 16 17:25:09 UTC 2022 , Edited by admin on Fri Dec 16 17:25:09 UTC 2022
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
ANHYDROUS->SOLVATE |
|
||
|
PARENT -> SALT/SOLVATE |
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |
|