Identification

Name
Levobunolol
Accession Number
DB01210
Description

A nonselective beta-adrenoceptor antagonist used in the treatment of glaucoma.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 291.3853
Monoisotopic: 291.183443671
Chemical Formula
C17H25NO3
Synonyms
  • (-)-Bunolol
  • (S)-5-(3-((1,1-dimethylethyl)amino)-2-hydroxypropoxy)-3,4-dihydro-1(2H)-naphthalenone
  • Levobunolol
  • Levobunololum

Pharmacology

Indication

For lowering intraocular pressure (IOP) and may be used in patients with chronic open-angle glaucoma or ocular hypertension.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Levobunolol is an ophthalmic beta-blocker, equally effective at β(1)- and β(2)-receptor sites. Levobunolol reduces both elevated and normal IOP in patients with or without glaucoma. In patients with elevated IOP, levobunolol reduces mean IOP by approximately 25-40% from baseline. As the drug is a nonselective &beta-adrenergic blocking agent, it can produce both systemic pulmonary and cardiovascular effects following topical application to the eye. These effects include adverse pulmonary effects (eg. bronchoconstriction, increased airway resistance), and a decrease in blood pressure and heart rate.

Mechanism of action

Levobunolol's mechanism of action in reducing IOP is not clearly defined, but is believed to be due to a reduction of the production of aqueous humor via blockage of endogenous catecholamine-stimulated increases in cyclic adenosine monophosphate (AMP) concentrations within the ciliary processes.

TargetActionsOrganism
ABeta-2 adrenergic receptor
antagonist
Humans
ABeta-1 adrenergic receptor
antagonist
Humans
Absorption

80%

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic

Route of elimination
Not Available
Half-life

20 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Bradycardia, hypotension, bronchospasm, and acute cardiac failure, LD50=700 mg/kg (orally in rat).

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Levobunolol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AvanafilThe risk or severity of hypotension can be increased when Avanafil is combined with Levobunolol.
DipyridamoleThe risk or severity of hypotension can be increased when Dipyridamole is combined with Levobunolol.
DronedaroneThe metabolism of Levobunolol can be decreased when combined with Dronedarone.
EscitalopramThe serum concentration of Levobunolol can be increased when it is combined with Escitalopram.
FluoxetineThe serum concentration of Levobunolol can be increased when it is combined with Fluoxetine.
FostamatinibThe risk or severity of hypotension can be increased when Fostamatinib is combined with Levobunolol.
GivosiranThe serum concentration of Levobunolol can be increased when it is combined with Givosiran.
HaloperidolThe serum concentration of Levobunolol can be increased when it is combined with Haloperidol.
LasmiditanLasmiditan may increase the bradycardic activities of Levobunolol.
MethimazoleThe excretion of Levobunolol can be decreased when combined with Methimazole.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

Product Ingredients
IngredientUNIICASInChI Key
Levobunolol hydrochlorideO90S49LDHH27912-14-7DNTDOBSIBZKFCP-YDALLXLXSA-N
International/Other Brands
Akbeta
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BetaganSolution / drops5 mg/1mLOphthalmicPhysicians Total Care, Inc.1986-07-242010-06-30US flag
BetaganSolution / drops5 mg/1mLOphthalmicAllergan, Inc.1986-07-24Not applicableUS flag
BetaganSolution / drops5 mg/1mLOphthalmicPhysicians Total Care, Inc.1986-07-242012-06-30US flag
BetaganSolution2.5 mg/1mLOphthalmicAllergan, Inc.2006-03-032006-03-03US flag
Betagan 0.5% Ophthalmic SolLiquidOphthalmicAllergan1985-12-312020-02-21Canada flag
Betagan Oph Soln 0.25%LiquidOphthalmicAllergan1990-12-312017-07-26Canada flag
Levobunolol HydrochlorideSolution / drops2.5 mg/1mLOphthalmicBauch & Lomb Incorporated2008-04-162008-05-05US flag
Levobunolol Hydrochloride Ophthalmic SolutionLiquidOphthalmicAlcon, Inc.Not applicableNot applicableCanada flag
Levobunolol Hydrochloride Ophthalmic SolutionLiquidOphthalmicBausch & Lomb Inc1997-09-242003-07-14Canada flag
Levobunolol Hydrochloride Ophthalmic SolutionLiquidOphthalmicAlcon, Inc.Not applicableNot applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-levobunolol Ophthalmic Solution USP 0.25%LiquidOphthalmicApotex Corporation2000-02-21Not applicableCanada flag
Apo-levobunolol Ophthalmic Solution USP 0.5%LiquidOphthalmicApotex Corporation2000-02-21Not applicableCanada flag
Levobunolol HydrochlorideSolution2.5 mg/1mLOphthalmicApotex Corporation2000-08-032006-02-03US flag
Levobunolol HydrochlorideSolution5 mg/1mLOphthalmicSandoz Inc1997-01-302017-08-31US flag
Levobunolol HydrochlorideSolution / drops2.5 mg/1mLOphthalmicPacific Pharma, Inc.1997-07-152021-01-31US flag
Levobunolol HydrochlorideSolution / drops5 mg/1mLOphthalmicBausch & Lomb Incorporated1994-03-04Not applicableUS flag
Levobunolol HydrochlorideSolution / drops5 mg/1mLOphthalmicPhysicians Total Care, Inc.1995-02-23Not applicableUS flag
Levobunolol HydrochlorideSolution / drops5 mg/1mLOphthalmicPacific Pharma, Inc.1997-07-152021-01-31US flag
Novo-levobunolol - Liq 0.25%LiquidOphthalmicNovopharm Limited1996-07-302015-10-26Canada flag
Novo-levobunolol - Liq 0.5%LiquidOphthalmicNovopharm Limited1996-07-302015-10-26Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Probeta - Liq OphLevobunolol hydrochloride (0.5 %) + Dipivefrin hydrochloride (0.1 %)LiquidOphthalmicAllergan1996-08-302012-07-16Canada flag

Categories

ATC Codes
S01ED03 — Levobunolol
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as tetralins. These are polycyclic aromatic compounds containing a tetralin moiety, which consists of a benzene fused to a cyclohexane.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Tetralins
Sub Class
Not Available
Direct Parent
Tetralins
Alternative Parents
Aryl alkyl ketones / Alkyl aryl ethers / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
1,2-aminoalcohol / Alcohol / Alkyl aryl ether / Amine / Aromatic homopolycyclic compound / Aryl alkyl ketone / Aryl ketone / Ether / Hydrocarbon derivative / Ketone
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
cyclic ketone, aromatic ether, propanolamine (CHEBI:6438)

Chemical Identifiers

UNII
G6317AOI7K
CAS number
47141-42-4
InChI Key
IXHBTMCLRNMKHZ-LBPRGKRZSA-N
InChI
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
IUPAC Name
5-[(2S)-3-(tert-butylamino)-2-hydroxypropoxy]-1,2,3,4-tetrahydronaphthalen-1-one
SMILES
CC(C)(C)NC[[email protected]](O)COC1=CC=CC2=C1CCCC2=O

References

General References
  1. Ishibashi T, Yokoi N, Kinoshita S: Comparison of the effects of topical levobunolol and timolol solution on the human ocular surface. Cornea. 2003 Nov;22(8):709-15. [PubMed:14576520]
  2. Ogasawara H, Yoshida A, Fujio N, Konno S, Ishiko S: [Effect of topical levobunolol on retinal, optic nerve head, and choroidal circulation in normal volunteers]. Nippon Ganka Gakkai Zasshi. 1999 Jul;103(7):544-50. [PubMed:10443129]
  3. Leung M, Grunwald JE: Short-term effects of topical levobunolol on the human retinal circulation. Eye (Lond). 1997;11 ( Pt 3):371-6. [PubMed:9373479]
  4. Dong Y, Ishikawa H, Wu Y, Yoshitomi T: Vasodilatory mechanism of levobunolol on vascular smooth muscle cells. Exp Eye Res. 2007 Jun;84(6):1039-46. Epub 2007 Jan 27. [PubMed:17459374]
  5. Gonzalez JP, Clissold SP: Ocular levobunolol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs. 1987 Dec;34(6):648-61. [PubMed:2892662]
  6. Lesar TS: Comparison of ophthalmic beta-blocking agents. Clin Pharm. 1987 Jun;6(6):451-63. [PubMed:2891463]
  7. Novack GD: Levobunolol for the long-term treatment of glaucoma. Gen Pharmacol. 1986;17(4):373-7. [PubMed:3019819]
Human Metabolome Database
HMDB0015341
KEGG Compound
C07914
PubChem Compound
39468
PubChem Substance
46507518
ChemSpider
36089
RxNav
1813
ChEBI
6438
ChEMBL
CHEMBL1201237
ZINC
ZINC000003830339
Therapeutic Targets Database
DAP000303
PharmGKB
PA164747027
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Levobunolol
AHFS Codes
  • 52:40.08 — Beta-adrenergic Agents
FDA label
Download (850 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Alcon Laboratories
  • Allergan Inc.
  • Apotex Inc.
  • Bausch & Lomb Inc.
  • Dispensing Solutions
  • Falcon Pharmaceuticals Ltd.
  • Novex Pharma
  • Pacific Pharma Lp
  • Pharmedix
  • Physicians Total Care Inc.
  • Prescript Pharmaceuticals
Dosage Forms
FormRouteStrength
LiquidOphthalmic
SolutionOphthalmic2.5 mg/1mL
SolutionOphthalmic5 mg/1mL
Solution / dropsOphthalmic2.5 mg/1mL
Solution / dropsOphthalmic5 mg/1mL
LiquidOphthalmic
SolutionOphthalmic
Solution / dropsOphthalmic1 MG/ML
Solution / dropsOphthalmic2.5 MG/ML
Solution / dropsOphthalmic5 MG/ML
Solution / dropsOphthalmic0.5 %
Prices
Unit descriptionCostUnit
Levobunolol HCl 0.5% Solution 15ml Bottle50.25USD bottle
Levobunolol HCl 0.5% Solution 10ml Bottle33.58USD bottle
Levobunolol HCl 0.25% Solution 10ml Bottle32.59USD bottle
Levobunolol HCl 0.5% Solution 5ml Bottle17.26USD bottle
Levobunolol HCl 0.25% Solution 5ml Bottle16.45USD bottle
Betagan 0.5% Solution6.39USD ml
Betagan 0.5% eye drops6.1USD ml
Betagan 0.25% eye drops4.9USD ml
Betagan 0.5 % Solution3.7USD ml
Levobunolol 0.5% eye drops3.24USD ml
Levobunolol 0.25% eye drops2.83USD ml
Pms-Levobunolol 0.5 % Solution1.63USD ml
Ratio-Levobunolol 0.5 % Solution1.63USD ml
Sandoz Levobunolol 0.5 % Solution1.63USD ml
Ratio-Levobunolol 0.25 % Solution1.23USD ml
Sandoz Levobunolol 0.25 % Solution1.23USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)209-211 °CNot Available
logP2.40HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.251 mg/mLALOGPS
logP2.06ALOGPS
logP2.18ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.66ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.56 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity83.28 m3·mol-1ChemAxon
Polarizability33.38 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9923
Blood Brain Barrier-0.8738
Caco-2 permeable-0.6105
P-glycoprotein substrateSubstrate0.8227
P-glycoprotein inhibitor IInhibitor0.5712
P-glycoprotein inhibitor IINon-inhibitor0.5691
Renal organic cation transporterNon-inhibitor0.8179
CYP450 2C9 substrateNon-substrate0.7696
CYP450 2D6 substrateSubstrate0.8547
CYP450 3A4 substrateNon-substrate0.5554
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8378
Ames testNon AMES toxic0.8825
CarcinogenicityNon-carcinogens0.9039
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.1253 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9613
hERG inhibition (predictor II)Inhibitor0.593
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Quast U, Vollmer KO: Binding of beta-adrenoceptor antagonists to rat and rabbit lung: special reference to levobunolol. Arzneimittelforschung. 1984;34(5):579-84. [PubMed:6147147]
  3. Sharif NA, Xu SX, Crider JY, McLaughlin M, Davis TL: Levobetaxolol (Betaxon) and other beta-adrenergic antagonists: preclinical pharmacology, IOP-lowering activity and sites of action in human eyes. J Ocul Pharmacol Ther. 2001 Aug;17(4):305-17. [PubMed:11572462]
  4. Harris A, Malinovsky V, Martin B: Correlates of acute exercise-induced ocular hypotension. Invest Ophthalmol Vis Sci. 1994 Oct;35(11):3852-7. [PubMed:7928182]
  5. Brooks AM, Gillies WE: Ocular beta-blockers in glaucoma management. Clinical pharmacological aspects. Drugs Aging. 1992 May-Jun;2(3):208-21. [PubMed:1351412]
  6. Gonzalez JP, Clissold SP: Ocular levobunolol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs. 1987 Dec;34(6):648-61. [PubMed:2892662]
  7. Lesar TS: Comparison of ophthalmic beta-blocking agents. Clin Pharm. 1987 Jun;6(6):451-63. [PubMed:2891463]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Lesar TS: Comparison of ophthalmic beta-blocking agents. Clin Pharm. 1987 Jun;6(6):451-63. [PubMed:2891463]
  2. Harris A, Malinovsky V, Martin B: Correlates of acute exercise-induced ocular hypotension. Invest Ophthalmol Vis Sci. 1994 Oct;35(11):3852-7. [PubMed:7928182]
  3. Chidlow G, Melena J, Osborne NN: Betaxolol, a beta(1)-adrenoceptor antagonist, reduces Na(+) influx into cortical synaptosomes by direct interaction with Na(+) channels: comparison with other beta-adrenoceptor antagonists. Br J Pharmacol. 2000 Jun;130(4):759-66. [PubMed:10864881]
  4. Sharif NA, Xu SX, Crider JY, McLaughlin M, Davis TL: Levobetaxolol (Betaxon) and other beta-adrenergic antagonists: preclinical pharmacology, IOP-lowering activity and sites of action in human eyes. J Ocul Pharmacol Ther. 2001 Aug;17(4):305-17. [PubMed:11572462]
  5. Brooks AM, Gillies WE: Ocular beta-blockers in glaucoma management. Clinical pharmacological aspects. Drugs Aging. 1992 May-Jun;2(3):208-21. [PubMed:1351412]
  6. Gonzalez JP, Clissold SP: Ocular levobunolol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs. 1987 Dec;34(6):648-61. [PubMed:2892662]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Sternieri E, Coccia CP, Pinetti D, Guerzoni S, Ferrari A: Pharmacokinetics and interactions of headache medications, part II: prophylactic treatments. Expert Opin Drug Metab Toxicol. 2006 Dec;2(6):981-1007. doi: 10.1517/17425255.2.6.981 . [PubMed:17125412]
  2. Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [PubMed:14732961]
  3. Iwaki M, Niwa T, Bandoh S, Itoh M, Hirose H, Kawase A, Komura H: Application of substrate depletion assay to evaluation of CYP isoforms responsible for stereoselective metabolism of carvedilol. Drug Metab Pharmacokinet. 2016 Dec;31(6):425-432. doi: 10.1016/j.dmpk.2016.08.007. Epub 2016 Sep 2. [PubMed:27836712]

Drug created on June 13, 2005 07:24 / Updated on September 17, 2020 23:29

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