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Identification
NameLevobunolol
Accession NumberDB01210  (APRD00165)
TypeSmall Molecule
GroupsApproved
Description

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

Structure
Thumb
Synonyms
(-)-Bunolol
(S)-5-(3-((1,1-Dimethylethyl)amino)-2-hydroxypropoxy)-3,4-dihydro-1(2H)-naphthalenone
Levobunolol
Levobunololum
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Betagansolution/ drops5 mg/mLophthalmicAllergan, Inc.1986-07-24Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Betagan 0.5% Ophthalmic Solliquid5 mgophthalmicAllergan Inc1985-12-31Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Betagan Oph Soln 0.25%liquid0.25 %ophthalmicAllergan Inc1990-12-31Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Levobunolol Hydrochloridesolution/ drops5 mg/mLophthalmicPacific Pharma, Inc.1997-07-15Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Levobunolol Hydrochloride Ophthalmic Solutionliquid0.50 %ophthalmicAlcon Canada IncNot applicableNot applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Levobunolol Hydrochloride Ophthalmic Solutionliquid0.25 %ophthalmicAlcon Canada IncNot applicableNot applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Levobunolol Hydrochloride Ophthalmic Solutionliquid0.50 %ophthalmicBausch & Lomb Pharmaceuticals Inc.1997-09-242003-07-14Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Levobunolol Hydrochloride Ophthalmic Solutionliquid0.25 %ophthalmicBausch & Lomb Pharmaceuticals Inc.1997-09-242003-07-14Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Novo-levobunolol - Liq 0.25%liquid0.25 %ophthalmicNovopharm Limited1996-07-302015-10-26Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Novo-levobunolol - Liq 0.5%liquid0.5 %ophthalmicNovopharm Limited1996-07-302015-10-26Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
PMS-levobunololliquid0.25 %ophthalmicPharmascience IncNot applicableNot applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
PMS-levobunololliquid0.5 %ophthalmicPharmascience Inc1998-08-31Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Ratio-levobunololsolution0.5 %ophthalmicTeva Canada Limited1995-12-31Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Ratio-levobunololsolution0.25 %ophthalmicTeva Canada Limited1995-12-31Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Sandoz Levobunololliquid0.25 %ophthalmicSandoz Canada Incorporated2000-08-21Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Sandoz Levobunololliquid0.5 %ophthalmicSandoz Canada Incorporated2000-08-21Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-levobunolol Ophthalmic Solution USP 0.25%liquid0.25 %ophthalmicApotex Inc2000-02-21Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Apo-levobunolol Ophthalmic Solution USP 0.5%liquid0.5 %ophthalmicApotex Inc2000-02-21Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Levobunolol Hydrochloridesolution/ drops5 mg/mLophthalmicBausch & Lomb Incorporated1994-03-04Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Levobunolol Hydrochloridesolution5 mg/mLophthalmicSandoz Inc1997-01-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Levobunolol Hydrochloridesolution/ drops5 mg/mLophthalmicPhysicians Total Care, Inc.1995-02-23Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Levobunolol Hydrochloridesolution/ drops2.5 mg/mLophthalmicBausch & Lomb Incorporated1994-03-04Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
AkbetaNot Available
Brand mixtures
NameLabellerIngredients
Probeta - Liq OphAllergan Inc
Salts
Name/CASStructureProperties
Levobunolol Hydrochloride
27912-14-7
Thumb
  • InChI Key: DNTDOBSIBZKFCP-YDALLXLXSA-N
  • Monoisotopic Mass: 327.16012141
  • Average Mass: 327.846
DBSALT000251
Categories
UNIIG6317AOI7K
CAS number47141-42-4
WeightAverage: 291.3853
Monoisotopic: 291.183443671
Chemical FormulaC17H25NO3
InChI KeyInChIKey=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[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
PathwaysNot Available
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 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 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Solution/ dropsophthalmic5 mg/mL
Liquidophthalmic5 mg
Liquidophthalmic0.25 %
Solutionophthalmic5 mg/mL
Solution/ dropsophthalmic2.5 mg/mL
Liquidophthalmic0.50 %
Liquidophthalmic0.5 %
Liquidophthalmic
Solutionophthalmic0.25 %
Solutionophthalmic0.5 %
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.
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 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
  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
AcetylcholineThe risk or severity of adverse effects can be increased when Levobunolol is combined with Acetylcholine.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Levobunolol.
BretyliumBretylium may increase the bradycardic activities of Levobunolol.
BupivacaineThe serum concentration of Bupivacaine can be increased when it is combined with Levobunolol.
ButabarbitalButabarbital may increase the hypotensive activities of Levobunolol.
ButethalButethal may increase the hypotensive activities of Levobunolol.
CabergolineLevobunolol may increase the vasoconstricting activities of Cabergoline.
CarbacholThe risk or severity of adverse effects can be increased when Levobunolol is combined with Carbachol.
CeritinibLevobunolol may increase the bradycardic activities of Ceritinib.
DronedaroneDronedarone may increase the bradycardic activities of Levobunolol.
DuloxetineLevobunolol may increase the orthostatic hypotensive activities of Duloxetine.
EsmololEsmolol may increase the bradycardic activities of Levobunolol.
FingolimodLevobunolol may increase the bradycardic activities of Fingolimod.
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Levobunolol.
HeptabarbitalHeptabarbital may increase the hypotensive activities of Levobunolol.
HexobarbitalHexobarbital may increase the hypotensive activities of Levobunolol.
IvabradineLevobunolol may increase the bradycardic activities of Ivabradine.
LacosamideLevobunolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
LevodopaLevobunolol may increase the orthostatic hypotensive activities of Levodopa.
LidocaineThe serum concentration of Lidocaine can be increased when it is combined with Levobunolol.
MepivacaineThe serum concentration of Mepivacaine can be increased when it is combined with Levobunolol.
MethacholineThe risk or severity of adverse effects can be increased when Levobunolol is combined with Methacholine.
MethohexitalMethohexital may increase the hypotensive activities of Levobunolol.
MidodrineLevobunolol may increase the bradycardic activities of Midodrine.
NicorandilNicorandil may increase the hypotensive activities of Levobunolol.
NifedipineNifedipine may increase the hypotensive activities of Levobunolol.
OctreotideOctreotide may increase the bradycardic activities of Levobunolol.
OrciprenalineLevobunolol may decrease the activities of Orciprenaline.
PentobarbitalPentobarbital may increase the hypotensive activities of Levobunolol.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Levobunolol.
PrimidonePrimidone may increase the hypotensive activities of Levobunolol.
RegorafenibRegorafenib may increase the bradycardic activities of Levobunolol.
ReserpineReserpine may increase the hypotensive activities of Levobunolol.
RisperidoneLevobunolol may increase the hypotensive activities of Risperidone.
RivastigmineRivastigmine may increase the bradycardic activities of Levobunolol.
RuxolitinibRuxolitinib may increase the bradycardic activities of Levobunolol.
SecobarbitalSecobarbital may increase the hypotensive activities of Levobunolol.
SufentanilSufentanil may increase the bradycardic activities of Levobunolol.
TheophyllineLevobunolol may decrease the activities of Theophylline.
TofacitinibTofacitinib may increase the bradycardic activities of Levobunolol.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Levobunolol.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Levobunolol.
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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13