You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameLevobunolol
Accession NumberDB01210  (APRD00165)
TypeSmall Molecule
GroupsApproved
Description

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

Structure
Thumb
Synonyms
SynonymLanguageCode
(-)-BunololNot AvailableNot Available
(S)-5-(3-((1,1-Dimethylethyl)amino)-2-hydroxypropoxy)-3,4-dihydro-1(2H)-naphthalenoneNot AvailableNot Available
LevobunololNot AvailableNot Available
LevobunololumLatinINN
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Betagansolution/ drops5 mg/mLophthalmicAllergan, Inc.1986-07-24Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Levobunolol Hydrochloridesolution/ drops5 mg/mLophthalmicPacific Pharma, Inc.1997-07-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Levobunolol Hydrochloridesolution/ drops5 mg/mLophthalmicBausch & Lomb Incorporated1994-03-04Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Levobunolol Hydrochloridesolution/ drops2.5 mg/mLophthalmicBausch & Lomb Incorporated1994-03-04Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Levobunolol Hydrochloridesolution/ drops5 mg/mLophthalmicPhysicians Total Care, Inc.1995-02-23Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Levobunolol Hydrochloridesolution5 mg/mLophthalmicSandoz Inc1997-01-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
AkbetaNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Levobunolol Hydrochloride
27912-14-7
Thumb
  • InChI Key: DNTDOBSIBZKFCP-YDALLXLXSA-N
  • Monoisotopic Mass: 327.16012141
  • Average Mass: 327.846
DBSALT000251
Categories
CAS number47141-42-4
WeightAverage: 291.3853
Monoisotopic: 291.183443671
Chemical FormulaC17H25NO3
InChI KeyIXHBTMCLRNMKHZ-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[C@H](O)COC1=CC=CC2=C1CCCC2=O
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassTetralins
Sub ClassNot Available
Direct ParentTetralins
Alternative Parents
Substituents
  • Tetralin
  • Aryl alkyl ketone
  • Aryl ketone
  • Alkyl aryl ether
  • Secondary alcohol
  • Ketone
  • 1,2-aminoalcohol
  • Secondary amine
  • Ether
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationFor lowering intraocular pressure (IOP) and may be used in patients with chronic open-angle glaucoma or ocular hypertension.
PharmacodynamicsLevobunolol 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 actionLevobunolol'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.
Absorption80%
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic

Route of eliminationNot Available
Half life20 hours
ClearanceNot Available
ToxicityBradycardia, hypotension, bronchospasm, and acute cardiac failure, LD50=700 mg/kg (orally in rat).
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Levobunolol Action PathwayDrug actionSMP00666
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrateNon-inhibitor0.9071
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateNon-inhibitor0.9025
CYP450 3A4 substrateNon-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
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Solutionophthalmic5 mg/mL
Solution/ dropsophthalmic2.5 mg/mL
Solution/ dropsophthalmic5 mg/mL
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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point209-211 °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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  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
  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
  3. Leung M, Grunwald JE: Short-term effects of topical levobunolol on the human retinal circulation. Eye. 1997;11 ( Pt 3):371-6. Pubmed
  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
  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
  6. Lesar TS: Comparison of ophthalmic beta-blocking agents. Clin Pharm. 1987 Jun;6(6):451-63. Pubmed
  7. Novack GD: Levobunolol for the long-term treatment of glaucoma. Gen Pharmacol. 1986;17(4):373-7. Pubmed
External Links
ATC CodesS01ED03
AHFS Codes
  • 52:92.00
PDB EntriesNot Available
FDA labelDownload (850 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetylcholineBeta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction.
BretyliumMay enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents.
BupivacaineBeta-Blockers may increase the serum concentration of Bupivacaine.
ButabarbitalMay enhance the hypotensive effect of Hypotensive Agents.
ButethalMay enhance the hypotensive effect of Hypotensive Agents.
CarbacholBeta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction.
DronedaroneMay enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6.
DuloxetineHypotensive Agents may enhance the orthostatic hypotensive effect of DULoxetine.
FingolimodBeta-Blockers may enhance the bradycardic effect of Fingolimod.
FloctafenineMay enhance the adverse/toxic effect of Beta-Blockers.
HeptabarbitalMay enhance the hypotensive effect of Hypotensive Agents.
HexobarbitalMay enhance the hypotensive effect of Hypotensive Agents.
LacosamideBradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide.
MepivacaineBeta-Blockers may increase the serum concentration of Mepivacaine.
MethacholineBeta-Blockers may enhance the adverse/toxic effect of Methacholine.
MethohexitalMay enhance the hypotensive effect of Hypotensive Agents.
MidodrineBeta-Blockers may enhance the bradycardic effect of Midodrine.
PentobarbitalMay enhance the hypotensive effect of Hypotensive Agents.
PrimidoneMay enhance the hypotensive effect of Hypotensive Agents.
RegorafenibMay enhance the bradycardic effect of Beta-Blockers.
ReserpineMay enhance the hypotensive effect of Beta-Blockers.
RisperidoneHypotensive Agents may enhance the hypotensive effect of RisperiDONE.
RivastigmineMay enhance the bradycardic effect of Beta-Blockers.
RuxolitinibMay enhance the bradycardic effect of Bradycardia-Causing Agents.
SecobarbitalMay enhance the hypotensive effect of Hypotensive Agents.
TofacitinibMay enhance the bradycardic effect of Bradycardia-Causing Agents.
Food InteractionsNot Available

Targets

1. Beta-1 adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Beta-1 adrenergic receptor P08588 Details

References:

  1. Lesar TS: Comparison of ophthalmic beta-blocking agents. Clin Pharm. 1987 Jun;6(6):451-63. Pubmed
  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
  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
  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
  5. Brooks AM, Gillies WE: Ocular beta-blockers in glaucoma management. Clinical pharmacological aspects. Drugs Aging. 1992 May-Jun;2(3):208-21. Pubmed
  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

2. Beta-2 adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Beta-2 adrenergic receptor P07550 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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
  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
  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
  5. Brooks AM, Gillies WE: Ocular beta-blockers in glaucoma management. Clinical pharmacological aspects. Drugs Aging. 1992 May-Jun;2(3):208-21. Pubmed
  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
  7. Lesar TS: Comparison of ophthalmic beta-blocking agents. Clin Pharm. 1987 Jun;6(6):451-63. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13