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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
SynonymLanguageCode
LevobunololumLatinINN
Salts
Name/CAS Structure Properties
Levobunolol Hydrochloride
27912-14-7
Thumb
  • InChI Key: DNTDOBSIBZKFCP-YDALLXLXSA-N
  • Monoisotopic Mass: 327.16012141
  • Average Mass: 327.846
DBSALT000251
Brand names
NameCompany
AkbetaNot Available
BetaganNot Available
Brand mixturesNot Available
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassTetralins
SubclassNot Available
Direct parentTetralins
Alternative parentsPhenol Ethers; Alkyl Aryl Ethers; Ketones; 1,2-Aminoalcohols; Secondary Alcohols; Dialkylamines; Polyamines
Substituentsphenol ether; alkyl aryl ether; benzene; 1,2-aminoalcohol; ketone; secondary alcohol; secondary amine; secondary aliphatic amine; ether; polyamine; amine; carbonyl group; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the tetralins. These are polycyclic aromatic compounds containing a tetralin moiety, which consists of a benzene fused to a cyclohexane.
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
Property Value Probability
Human Intestinal Absorption + 0.9923
Blood Brain Barrier - 0.8738
Caco-2 permeable - 0.6105
P-glycoprotein substrate Substrate 0.8227
P-glycoprotein inhibitor I Inhibitor 0.5712
P-glycoprotein inhibitor II Non-inhibitor 0.5691
Renal organic cation transporter Non-inhibitor 0.8179
CYP450 2C9 substrate Non-substrate 0.7696
CYP450 2D6 substrate Substrate 0.8547
CYP450 3A4 substrate Non-substrate 0.5554
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8378
Ames test Non AMES toxic 0.8825
Carcinogenicity Non-carcinogens 0.9039
Biodegradation Not ready biodegradable 0.9972
Rat acute toxicity 2.1253 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9613
hERG inhibition (predictor II) Inhibitor 0.593
Pharmacoeconomics
Manufacturers
  • Akorn inc
  • Allergan pharmaceutical
  • Bausch and lomb pharmaceuticals inc
  • Falcon pharmaceuticals ltd
  • Novex pharma
Packagers
Dosage forms
FormRouteStrength
LiquidOphthalmic
SolutionOphthalmic
Prices
Unit descriptionCostUnit
Levobunolol HCl 0.5% Solution 15ml Bottle50.25USDbottle
Levobunolol HCl 0.5% Solution 10ml Bottle33.58USDbottle
Levobunolol HCl 0.25% Solution 10ml Bottle32.59USDbottle
Levobunolol HCl 0.5% Solution 5ml Bottle17.26USDbottle
Levobunolol HCl 0.25% Solution 5ml Bottle16.45USDbottle
Betagan 0.5% Solution6.39USDml
Betagan 0.5% eye drops6.1USDml
Betagan 0.25% eye drops4.9USDml
Betagan 0.5 % Solution3.7USDml
Levobunolol 0.5% eye drops3.24USDml
Levobunolol 0.25% eye drops2.83USDml
Pms-Levobunolol 0.5 % Solution1.63USDml
Ratio-Levobunolol 0.5 % Solution1.63USDml
Sandoz Levobunolol 0.5 % Solution1.63USDml
Ratio-Levobunolol 0.25 % Solution1.23USDml
Sandoz Levobunolol 0.25 % Solution1.23USDml
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 solubility2.51e-01 g/lALOGPS
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 area58.56ChemAxon
rotatable bond count6ChemAxon
refractivity83.28ChemAxon
polarizability33.38ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
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
ResourceLink
KEGG CompoundC07914
PubChem Compound39468
PubChem Substance46507518
ChemSpider36089
ChEBI6438
ChEMBLCHEMBL1201237
Therapeutic Targets DatabaseDAP000303
PharmGKBPA164747027
Drug Product Database2241575
RxListhttp://www.rxlist.com/cgi/generic/levobunolol.htm
Drugs.comhttp://www.drugs.com/cdi/levobunolol-drops.html
WikipediaLevobunolol
ATC CodesS01ED03
AHFS Codes
  • 52:92.00
PDB EntriesNot Available
FDA labelshow(850 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food InteractionsNot Available

Targets

1. 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

2. 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

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