Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C13H24N4O3S |
Molecular Weight | 316.4213 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)(C)NC[C@@]([H])(COc1c(nsn1)N2CCOCC2)O
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 | 316.4213 |
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 |
---|---|---|
Attenuation of hydrochlorothiazide-induced hypokalemia in dogs by a beta-adrenergic blocking drug, timolol. | 1975 Jun-Jul |
|
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 |
|
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 |
|
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 |
|
[Timolol: adverse cardiorespiratory effects]. | 1989 May |
|
Depression associated with diltiazem. | 1989 Sep 23 |
|
[Raynaud syndrome following timolol-containing eyedrops]. | 1990 |
|
Apraclonidine hydrochloride: an evaluation of plasma concentrations, and a comparison of its intraocular pressure lowering and cardiovascular effects to timolol maleate. | 1990 |
|
Complete heart block after topical timolol. | 1990 Aug |
|
Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine. | 1990 Sep |
|
[Bradycardia of an elderly patient caused by Timolol therapy in ocular hypertension]. | 1996 |
|
Plasma timolol concentrations of timolol maleate: timolol gel-forming solution (TIMOPTIC-XE) once daily versus timolol maleate ophthalmic solution twice daily. | 2001 Jul |
|
[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 |
|
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 |
|
Third degree AC block due to ophthalmic timilol solution. | 2001 Sep-Oct |
|
One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular hypertension. | 2002 Oct |
|
Topical beta blockers and atrioventricular block in the elderly. | 2002 Oct-Dec |
|
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 |
|
Readability of ocular medication inserts. | 2003 Feb |
|
Comparison of efficacy and tolerability between two gel-forming timolol maleate ophthalmic solutions in patients with glaucoma or ocular hypertension. | 2003 Jan-Feb |
|
[A combination of timoptol and L-arginine HCl: a regulator of intraocular pressure in rabbits]. | 2003 Sep |
|
Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma. | 2004 Sep |
|
[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 |
|
Types of Glaucoma and recent trends applied in treatment: Observations from a Glaucoma Training Workshop in the Gambia. | 2005 Sep |
|
[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 |
|
[Effect of the mixture of timoptol and amino acid taurine in the bioregulation of the intraocular pressure in rabbits]. | 2007 Jul |
|
Effects of topical antiglaucoma medications on corneal epithelium as evaluated by gene expression patterns. | 2007 Oct |
|
A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. | 2007 Oct 16 |
|
Cost analysis of glaucoma medications. | 2008 Jan |
|
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 |
|
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 |
|
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 |
|
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 |
|
Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells. | 2010 Oct 21 |
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
Sat Jun 26 15:37:22 UTC 2021
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Record UNII |
5JKY92S7BR
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Record Status |
Validated (UNII)
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Record Version |
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N0000000161
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C07AA06
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N0000175556
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S01ED01
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NCI_THESAURUS |
C29576
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3415
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M10871
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C90802
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1546004
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33624
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DB00373
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6533
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SUB11069MIG
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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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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 |
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 |