LEVOBUNOLOL HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H25NO3.ClH
Molecular Weight	327.846
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CC(C)(C)NC[C@H](O)COC1=CC=CC2=C1CCCC2=O

InChI

InChIKey=DNTDOBSIBZKFCP-YDALLXLXSA-N

InChI=1S/C17H25NO3.ClH/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;1H/t12-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C17H25NO3
Molecular Weight	291.3853
Charge	0
Count

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

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 203 Target ID: CHEMBL210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11572462	Antagonist 2778		0.76 nM [Ki]
Beta-1 adrenergic receptor 158 Target ID: CHEMBL213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11572462	Antagonist 2778		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 8429	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 1985
Chronic open-angle glaucoma 6 Sources: http://www.allergan.com/assets/pdf/betagan_pi	Primary		Approved 8429	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 1985

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
[Effect of topical levobunolol on retinal, optic nerve head, and choroidal circulation in normal volunteers].	1999 Jul	10443129
False-negative patch test with levobunolol.	2001 Apr	11260243
Timolol may inhibit aqueous humor secretion by cAMP-independent action on ciliary epithelial cells.	2001 Sep	11502564
Cost analysis of glaucoma medications: a 3-year review.	2002 Aug	12169974
Spectrophotometric determination of beta-adrenergic blocking agents in pharmaceutical formulations.	2002 Jul 1	12062653
Thyroid eye disease and glaucoma.	2003 Dec	14646686
Noninvasive assessment of aqueous humor turnover in the mouse eye.	2003 Feb	12556404
Medical therapy cost considerations for glaucoma.	2003 Jul	12834665
The effect of topical glaucoma medications evaluated by perimetry.	2003 Jun	12770987
Bilateral nongranulomatous anterior uveitis associated with bimatoprost.	2003 Nov	14670442
Comparison of the effects of topical levobunolol and timolol solution on the human ocular surface.	2003 Nov	14576520
Metipranolol attenuates lipid peroxidation in rat brain: a comparative study with other antiglaucoma drugs.	2003 Oct	12898280
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
Effects of antiglaucoma drugs on cellular proliferation in cultured human corneal keratocytes.	2006 Mar	16602276
Transdermal delivery of beta-blockers.	2006 May	16640500
Drops and falls.	2006 Nov	17047012
Allergic contact dermatitis due to levobunolol with cross-sensitivity to befunolol.	2007 Jan	17177718
Vasodilatory mechanism of levobunolol on vascular smooth muscle cells.	2007 Jun	17459374
Miscellaneous.	2008 Oct	21593974
Recent advances in pharmacotherapy of glaucoma.	2008 Oct	20040958
Retrospective cohort study of 163 pediatric glaucoma patients.	2009 Jun	19491991
Efficacy and patient tolerability of travoprost BAK-free solution in patients with open-angle glaucoma and ocular hypertension.	2010 Aug 9	20714366
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 `Fri Dec 15 15:24:46 GMT 2023` Edited by `admin` on `Fri Dec 15 15:24:46 GMT 2023`
Record UNII	O90S49LDHH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEVOBUNOLOL HYDROCHLORIDE

Official Name

English

LEVOBUNOLOL HCL

Common Name

English

LEVOBUNOLOL HYDROCHLORIDE [VANDF]

Common Name

English

NSC-759158

Code

English

LEVOBUNOLOL HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

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

Systematic Name

English

BETAGAN

Brand Name

English

1(2H)-NAPHTHALENONE, 5-(3-((1,1-DIMETHYLETHYL)AMINO)-2-HYDROXYPROPOXY)-3,4-DIHYDRO-, HYDROCHLORIDE, (-)-(S)

Common Name

English

LEVOBUNOLOL HYDROCHLORIDE [JAN]

Common Name

English

W-7000A

Code

English

AKBETA

Brand Name

English

Levobunolol hydrochloride [WHO-DD]

Common Name

English

LEVOBUNOLOL HYDROCHLORIDE [MI]

Common Name

English

W 7000A

Code

English

LEVOBUNOLOL HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

LEVOBUNOLOL HYDROCHLORIDE [USAN]

Common Name

English

LEVOBUNOLOL HYDROCHLORIDE [USP-RS]

Common Name

English

LEVOBUNOLOL HYDROCHLORIDE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29576