TIMOLOL ANHYDROUS

First approved in 1978

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

Structure Search

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

HIDE SMILES / InChI

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21516_istalol_lbl.pdf
Curator's Comment:: 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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Beta-2 adrenergic receptor 197 Target ID: CHEMBL210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2903243	Antagonist 2577	Glaucoma Open-angle glaucoma Ocular hypertension	0.200000000000000011 nM [Kd]
Beta-1 adrenergic receptor 157 Target ID: CHEMBL213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2903243	Antagonist 2577	Ocular hypertension Open-angle glaucoma Glaucoma	7.90000000000000036 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ocular hypertension 49 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21516_istalol_lbl.pdf	Primary	Beta-1 adrenergic receptor Beta-2 adrenergic receptor	Approved 7997	BETIMOL Approved Use Betimol® is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Launch Date 796608000000
Open-angle glaucoma 50 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21516_istalol_lbl.pdf	Primary	Beta-1 adrenergic receptor Beta-2 adrenergic receptor	Approved 7997	BETIMOL Approved Use Betimol® is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Launch Date 796608000000
Glaucoma 54 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021398s007lbl.pdf	Primary	Beta-1 adrenergic receptor Beta-2 adrenergic receptor	Approved 7997	BETIMOL Approved Use Betimol® is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Launch Date 796608000000

C_max

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

T_1/2

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 Dose: 1 drop, 2 times / day Route: ophthalmic Route: steady Dose: 1 drop, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019463s031lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019463s031lbl.pdf	Other AEs: Stinging... Other AEs: Stinging (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019463s031lbl.pdf

AEs

AE	Significance	Dose	Population
Stinging	1 patient	1 drop 2 times / day steady, ophthalmic Dose: 1 drop, 2 times / day Route: ophthalmic Route: steady Dose: 1 drop, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019463s031lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019463s031lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1038

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 231

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 231	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021516s000_Istalol_BioPharmr.pdf Page: 5	likely
CYP2D6 1038	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/18-086S052.pdf 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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/18-086S052.pdf Page: 7, 8, 19

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY427027
1PlusChem LLC	1P0038LF
1PlusChem LLC	1P006VQA
A2B Chem	AB50307
AK Scientific	U843
AK Scientific	W0079
APExBIO	B1350
AbovChem LLC	HY-17380
Alfa Chemistry	121908
Alfa Chemistry	ACM26839758
Alfa Chemistry	ACM26921175
Alfa Chemistry	ACM29023481
Alfa Chemistry	ACM33305952
Alfa Chemistry	ACM50929981
Angene	AGN-PC-0R2U1T
Aronis	BBC/645
AstaTech	F20622
Axon MedChem	1518
BLDpharm	BD42631
BOC Sciences	26839-75-8
BOC Sciences	26921-17-5
BOC Sciences	57073-55-9
BioSynth	Q-201837
BioSynth	W-107148
Bosche Scientific	T5568
Cayman Chemical	13974
Chem Scene	CS-1028
ChemShuttle	151881
Compound Cloud	33624
Compound Cloud	5281056
Compound Cloud	62933
Enamine	EN300-296015
Hairui	HR130502
Hairui	HR130770
Hangzhou Yuhao Chemical Technology	JZ5713
Hangzhou Yuhao Chemical Technology	RT4634
IBScreen	Bio-0875
Innovapharm	BBV-00092006
KeyOrganics	AS-18090
Lab Network	454
Lan Pharmatech	LQT-B48540
MedChem Express	HY-17380
MolPort	MolPort-006-125-123
MolPort	MolPort-046-842-946
Molcore	MC427027
Molnova	M13824
MuseChem	R009857
MuseChem	R017522
Norris Pharm	NSZB-A280026
Princeton BioMolecular Research	OSSL_857914
Princeton BioMolecular Research	PBMR221655
Ryan Scientific	Clopidogrel
Selleck Chemicals	S4123
Sigma Aldrich	1667406
Sigma Aldrich	1667406\|USP
Sigma Aldrich	BP1046
Sigma Aldrich	BP1046\|SIAL
Sigma Aldrich	T1450000
Sigma Aldrich	T1450000\|SIAL
Sigma Aldrich	T6394
Sigma Aldrich	T6394\|SIGMA
Sigma Aldrich	Y0001270
Sigma Aldrich	Y0001270\|SIAL
StruChem	SC-50864
TargetMol	T0475
Tetrahedron	TS09088
Tetrahedron	TS61295
TimTec	SBB116704
TimTec	ST072193
Tocris	649
Toronto Research Chemicals	T443700
Toronto Research Chemicals	T443703
Toronto Research Chemicals	T443710
Vitas-M Laboratory	BBL024494
Vitas-M Laboratory	STK087021
ZINC	ZINC000000002176	http://zinc15.docking.org/substances/ZINC000000002176
eMolecules	109712517
eMolecules	18591678
eMolecules	1933616
eMolecules	206903750
eMolecules	26749913
eMolecules	27315261
eMolecules	45915201
eMolecules	76746736
eMolecules	902584
mcule	MCULE-4835580308
mcule	MCULE-6341844618
mcule	MCULE-6525920865
mcule	MCULE-6845179708
mcule	MCULE-9403889753

PubMed

Title	Date	PubMed
Amelioration of bendrofluazide-induced hypokalemia by timolol.	1977 Jul	326460
[Timolol: adverse cardiorespiratory effects].	1989 May	2491593
Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine.	1990 Sep	2205182
[Bradyarrhythmias secondary to the use of ophthalmic timolol. A report of 3 cases].	1992 Jan	1549765
[A combination of timoptol and L-arginine HCl: a regulator of intraocular pressure in rabbits].	2003 Sep	14518356
[Effect of various anti-glaucoma eyedrops on human corneal epithelial cells].	2004 Feb	15022429
Antiglaucoma eye drop pulses--increased interleukin-6 secretion by Tenon's capsule fibroblast cultures.	2004 Jun	15118463
A case of clarithromycin-induced manic episode (antibiomania).	2004 Mar	14731313
Improvement of the ocular bioavailability of timolol by sorbic acid.	2004 Mar 19	15019072
[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	15307650
Binding of (-)-[3H]-CGP12177 at two sites in recombinant human beta 1-adrenoceptors and interaction with beta-blockers.	2004 May	15060759
Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma.	2004 Sep	15002024
Polymorphism of the bm86 gene in South American strains of the cattle tick Boophilus microplus.	2005	16323051
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	18217260
Reversal of laser in situ keratomileusis-induced ectasia with intraocular pressure reduction.	2005 Aug	16129306
The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors.	2005 Feb	15655528
Alphagan allergy may increase the propensity for multiple eye-drop allergy.	2005 Feb	15254495
[Economic impact of eyedrop cost in glaucoma treatment].	2005 Jan-Feb	15824808
Factors associated with readmission to a general hospital in Brazil.	2005 Jul-Aug	16021256
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
[The rabbit IOP and pupil values after application of aminoacid L-lysine and antiglaucomatic Timoptol mixture].	2005 Mar	15898332
Three cases of Descemet's membrane detachment after cataract surgery.	2005 Oct 31	16259074
Types of Glaucoma and recent trends applied in treatment: Observations from a Glaucoma Training Workshop in the Gambia.	2005 Sep	16160723
Syncope and falls due to timolol eye drops.	2006 Apr 22	16627515
[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	16491635
Prospective comparative switch study from timolol 0.5% and latanoprost 0.005% to bimatoprost 0.03%.	2006 Jan-Feb	16644608
[The effect of glycine with timoptol on the rabbit IOP physiological values].	2006 Jul	16895057
Atishoo! Atishoo! we all fall down!	2006 Jul	16788083
24-Hour control with a latanoprost-timolol fixed combination vs timolol alone.	2006 Nov	17102001
Hypotony and choroidal detachment as a complication of topical combined timolol and dorzolamide.	2007 Apr	17444809
Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on circadian intraocular pressure.	2007 Dec	17459480
Sinoatrial block induced by timolol eyedrops.	2007 Feb	17361266
[Effect of the mixture of timoptol and amino acid taurine in the bioregulation of the intraocular pressure in rabbits].	2007 Jul	17682602
Effects of topical antiglaucoma medications on corneal epithelium as evaluated by gene expression patterns.	2007 Oct	17881916
A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling.	2007 Oct 16	17925438
[Late postoperative choroidal detachment].	2008	18655461
Role of endogenous RGS proteins on endothelial ERK 1/2 activation.	2008 Dec	18977218
Efficacy and safety of latanoprost versus pilocarpine/timolol maleate fixed combination in patients with primary open-angle glaucoma or ocular hypertension.	2008 Dec	18721251
Optic atrophy, necrotizing anterior scleritis and keratitis presenting in association with Streptococcal Toxic Shock Syndrome: a case report.	2008 Feb 29	18312659
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	18166407
[Influence on tear film after instillation of timolol maleate ophthalmic gel-forming solution examination by a tear film stability analysis system].	2008 Jun	18592978
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	19668763
Role of fixed-combination brinzolamide 1%/timolol 0.5% in the treatment of elevated intraocular pressure in open-angle glaucoma and ocular hypertension.	2009	19898664
Oral versus topical carbonic anhydrase inhibitors in ocular hypertension after scleral tunnel cataract surgery.	2009	19668590
Cytochrome oxidase 2D6 gene polymorphism in primary open-angle glaucoma with various effects to ophthalmic timolol.	2009 Apr	19284319
Effect of latanoprost and timolol on the histopathology of the human conjunctiva.	2009 Feb	18971237
Effects of timolol-related ophthalmic solutions on cultured human conjunctival cells.	2010 Nov	21191725
Association of CYP2D6 single-nucleotide polymorphism with response to ophthalmic timolol in primary open-angle Glaucoma--a pilot study.	2010 Oct	20925579
Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells.	2010 Oct 21	21060675
Factors which influenced the decentralisation of leprosy control activities in the municipality of Betim, Minas Gerais State, Brazil.	2010 Sep	21067060

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Sat Jun 26 15:37:22 UTC 2021` Edited by `admin` on `Sat Jun 26 15:37:22 UTC 2021`
Record UNII	5JKY92S7BR
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

TIMOLOL ANHYDROUS

Common Name

English

2-PROPANOL, 1-((1,1-DIMETHYLETHYL)AMINO)-3-((4-(4-MORPHOLINYL)-1,2,5-THIADIAZOL-3-YL)OXY)-, (S)-

Systematic Name

English

TIMOLOL [INN]

Common Name

English

TIMOLOL [WHO-DD]

Common Name

English

TIMOLOL [HSDB]

Common Name

English

TIMOLOL [MI]

Common Name

English

2-PROPANOL, 1-((1,1-DIMETHYLETHYL)AMINO)-3-((4-(4-MORPHOLINYL)-1,2,5-THIADIAZOL-3-YL)OXY)-, (2S)-

Systematic Name

English

(S)-1-(TERT-BUTYLAMINO)-3-((4-MORPHOLINO-1,2,5-THIADIAZOL-3-YL)OXY)-2-PROPANOL

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000000161