LEVOBUNOLOL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H25NO3
Molecular Weight	291.3859
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])(COc1cccc2c1CCCC2=O)O

InChI

InChIKey=IXHBTMCLRNMKHZ-LBPRGKRZSA-N

InChI=1S/C17H25NO3/c1-17(2,3)18-10-12(19)11-21-16-9-5-6-13-14(16)7-4-8-15(13)20/h5-6,9,12,18-19H,4,7-8,10-11H2,1-3H3/t12-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C17H25NO3
Molecular Weight	291.3859
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.allergan.com/assets/pdf/betagan_pi
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11572462 | https://www.drugs.com/pro/levobunolol.html | https://www.ncbi.nlm.nih.gov/pubmed/3019819 | https://www.ncbi.nlm.nih.gov/pubmed/17459374

Levobunolol is a non-cardioselective beta-adrenoceptor blocking agent, equipotent at both beta1 and beta2 adrenergic receptors. Levobunolol is greater than 60 times more potent than its dextro isomer in its beta-blocking activity, yet equipotent in its potential for direct myocardial depression. Accordingly, the levo isomer, levobunolol, is used. Levobunolol does not have significant local anesthetic (membrane-stabilizing) or intrinsic sympathomimetic activity. Levobunolol, sold under the brand name Betagan, has been shown to be an active agent in lowering elevated as well as normal intraocular pressure (IOP) whether or not accompanied by glaucoma. Levobunolol is contraindicated in those individuals with bronchial asthma or with a history of bronchial asthma, or severe chronic obstructive pulmonary disease sinus bradycardia; second and third-degree atrioventricular block; overt cardiac failure cardiogenic shock; or hypersensitivity to any component of these products.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Beta-2 adrenergic receptor 194 Target ID: CHEMBL210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11572462	Antagonist 2575		0.76 nM [Ki]
Beta-1 adrenergic receptor 153 Target ID: CHEMBL213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11572462	Antagonist 2575		32.6 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ocular hypertension 50 Sources: http://www.allergan.com/assets/pdf/betagan_pi	Primary		Approved 8043	BETAGAN Approved Use BETAGAN ® ophthalmic solution has been shown to be effective in lowering intraocular pressure and may be used in patients with chronic open-angle glaucoma or ocular hypertension. Launch Date 5.03798399E11
Chronic open-angle glaucoma 6 Sources: http://www.allergan.com/assets/pdf/betagan_pi	Primary		Approved 8043	BETAGAN Approved Use BETAGAN ® ophthalmic solution has been shown to be effective in lowering intraocular pressure and may be used in patients with chronic open-angle glaucoma or ocular hypertension. Launch Date 5.03798399E11

C_max

Value	Dose	Co-administered	Analyte	Population
2.65 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/336256	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:		DIHYDROBUNOLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.72 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/336256	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:		LEVOBUNOLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
3.08 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3323465	410 μg single, intravenous dose: 410 μg route of administration: Intravenous experiment type: SINGLE co-administered:		LEVOBUNOLOL blood	Oryctolagus cuniculus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
7.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/336256	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROBUNOLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
42 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3323465	410 μg single, intravenous dose: 410 μg route of administration: Intravenous experiment type: SINGLE co-administered:	LEVOBUNOLOL blood	Oryctolagus cuniculus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/336256	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	LEVOBUNOLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
0.5 % 1 times / day steady, ophthalmic Recommended Dose: 0.5 %, 1 times / day Route: ophthalmic Route: steady Dose: 0.5 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019219s029lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: glaucoma Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019219s029lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019219s029lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6438	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6438
ZINC	ZINC000003830339	http://zinc15.docking.org/substances/ZINC000003830339

PubMed

Title	Date	PubMed
l-Bunolol and propranolol: oral and intravenous beta-adrenoceptor blocking activity in rats compared to dogs and humans.	1978 Jan	22739
Levobunolol for the long-term treatment of glaucoma.	1986	3019819
Ocular levobunolol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy.	1987 Dec	2892662
Comparison of ophthalmic beta-blocking agents.	1987 Jun	2891463
A comparison of the ocular tolerability of a single dose of timolol and levobunolol in healthy normotensive volunteers.	1993 Apr	8484654
A comparison of the ocular hypotensive efficacy and systemic safety of 0.5% levobunolol and 2% carteolol.	1994	8145982
Syncope, bradycardia, and atrioventricular block associated with topical ophthalmic levobunolol.	1994 Mar	8122621
Short-term effects of topical levobunolol on the human retinal circulation.	1997	9373479
Bilateral nongranulomatous anterior uveitis associated with bimatoprost.	2003 Nov	14670442
[Osmotic resistance of red blood cells membranes in Vermox and "AKbeta" vitamin complex treatment of experimental trichinosis in rats].	2004	16865965
Binding affinities of ocular hypotensive beta-blockers levobetaxolol, levobunolol, and timolol at endogenous guinea pig beta-adrenoceptors.	2004 Apr	15117564
Deposits in artificial corneas: risk factors and prevention.	2004 Apr	15068437
[Cost-effectivity analysis of the most used antiglaucoma drugs].	2004 Aug	15306964
Stereoselectivity for interactions of agonists and antagonists at mouse, rat and human beta3-adrenoceptors.	2004 Jan 26	14744619
Effects of carteolol hydrochloride on the in vitro production of LPS-induced proinflammatory cytokines by murine macrophage.	2004 Jun	15279728
Inhibition of endothelin-1 and KCL-induced increase of [CA2+]i by antiglaucoma drugs in cultured A7r5 vascular smooth-muscle cells.	2004 Jun	15279725
Reversal of disc cupping after intraocular pressure reduction in topographic image series.	2004 Oct	15354070
The effect of once-daily levobunolol on intraocular pressure in normal-tension glaucoma.	2005 Jan-Feb	15692777
Carteolol hydrochloride protects human corneal epithelial cells from UVB-induced damage in vitro.	2005 Mar	15725891
Study of effects of antiglaucoma eye drops on N-methyl-D-aspartate-induced retinal damage.	2005 Nov-Dec	16365790
Allergic contact dermatitis due to beta-blockers in eye drops: a retrospective analysis of multicentre surveillance data 1993-2004.	2006	17106597
Contact dermatitis to levobunolol eyedrops superimposed on IgE-mediated rhinoconjunctivitis.	2006 Dec	17201244
Effects of antiglaucoma drugs on calcium mobility in cultured corneal endothelial cells.	2006 Feb	16568722
Allergic contact dermatitis due to levobunolol in an ophthalmic preparation.	2006 Jul	16848829
The management of glaucoma and intraocular hypertension: current approaches and recent advances.	2006 Jun	18360593
Effects of antiglaucoma drugs on cellular proliferation in cultured human corneal keratocytes.	2006 Mar	16602276
Transdermal delivery of beta-blockers.	2006 May	16640500
Beta-blocker eye drops.	2006 May 30-Jun 5	16764382
Drops and falls.	2006 Nov	17047012
Myocilin mutations among primary open angle glaucoma patients of Kanyakumari district, South India.	2007 Apr 2	17417611
Allergic contact dermatitis due to levobunolol with cross-sensitivity to befunolol.	2007 Jan	17177718
Membrane electrodes for determination of some beta-blocker drugs.	2007 Jul-Aug	17760336
Levobetaxolol hydrochloride: a review of its pharmacology and use in the treatment of chronic open-angle glaucoma and ocular hypertension.	2007 Jun	19668496
Vasodilatory mechanism of levobunolol on vascular smooth muscle cells.	2007 Jun	17459374
Cellular cytotoxicity of antiglaucoma drugs in cultured corneal endothelial cells.	2007 Mar	17389174
Daily cost of glaucoma medications in China.	2007 Oct-Nov	18091176
An in vivo confocal microscopy and impression cytology analysis of preserved and unpreserved levobunolol-induced conjunctival changes.	2008 May-Jun	18465723
Miscellaneous.	2008 Oct	21593974
Recent advances in pharmacotherapy of glaucoma.	2008 Oct	20040958
Oral versus topical carbonic anhydrase inhibitors in ocular hypertension after scleral tunnel cataract surgery.	2009	19668590
Aerobic exercise and intraocular pressure in normotensive and glaucoma patients.	2009 Aug 13	19678955
Effect of latanoprost and timolol on the histopathology of the human conjunctiva.	2009 Feb	18971237
Poly (epsilon-caprolactone) microparticles containing Levobunolol HCl prepared by a multiple emulsion (W/O/W) solvent evaporation technique: effects of some formulation parameters on microparticle characteristics.	2009 Feb	18608798
Retrospective cohort study of 163 pediatric glaucoma patients.	2009 Jun	19491991
[Cytotoxicity of antiglaucoma ophthalmic solutions for human corneal endothelial cells].	2009 May	19489448
Comparison of effects of topical levobunolol to a combination of timolol-dorzolamide on intraocular pressure and pulse rate of healthy dogs.	2009 Sep	19626454
Efficacy and patient tolerability of travoprost BAK-free solution in patients with open-angle glaucoma and ocular hypertension.	2010 Aug 9	20714366
Effects of topical 0.5% levobunolol alone or in association with 2% dorzolamide compared with a fixed combination of 0.5% timolol and 2% dorzolamide on intraocular pressure and heart rate in dogs without glaucoma.	2010 Fall	20960417
A new mode of dimerization of allosteric enzymes with ACT domains revealed by the crystal structure of the aspartate kinase from Cyanobacteria.	2010 Jun 4	20398676
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541

Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting dose is one to two drops of BETAGAN (Levobunolol) ophthalmic solution 0.5% in the affected eye(s) once a day. Typical dosing with BETAGAN® 0.25% is one to two drops twice daily. In patients with more severe or uncontrolled glaucoma, BETAGAN® 0.5% can be administered b.i.d. As with any new medication, careful monitoring of patients is advised. Dosages above one drop of BETAGAN® 0.5% b.i.d. are not generally more effective.

Route of Administration: Topical

In Vitro Use Guide

The ability of levobunolol to relax ciliary artery rings pre-contracted with other agents, including phenylephrine and in Ca2+-free media was determined by isometric tension recording method. The pre-contraction was maintained for 20 min, then levobunolol was applied every 10 min in a cumulative manner. Levobunolol at 30 mkM and at 100 mkM significantly reduced the contractile response to phenylephrine.

Substance Class	Chemical Created by `admin` on `Sat Jun 26 10:46:40 UTC 2021` Edited by `admin` on `Sat Jun 26 10:46:40 UTC 2021`
Record UNII	G6317AOI7K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEVOBUNOLOL

Official Name

English

LEVOBUNOLOL [MI]

Common Name

English

LEVOBUNOLOL [VANDF]

Common Name

English

BUNOLOL, (S)-

Common Name

English

(-)-(S)-5-(3-(TERT-BUTYLAMINO)-2-HYDROXYPROPOXY)-3,4-DIHYDRO-1(2H)-NAPHTHALENONE

Systematic Name

English

LEVOBUNOLOL [INN]

Common Name

English

LEVOBUNOLOL [WHO-DD]

Common Name

English

BUNOLOL, (-)-

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175556