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Identification
NameNebivolol
Accession NumberDB04861
Typesmall molecule
Groupsapproved, investigational
Description

Nebivolol is a highly cardioselective vasodilatory beta1 receptor blocker used in treatment of hypertension. In most countries, this medication is available only by prescription. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
NebivololumLatinNot Available
Salts
Name/CAS Structure Properties
Nebivolol hydrochloride
Thumb Not applicable DBSALT001027
Brand names
NameCompany
BystolicNot Available
LobivonNot Available
NebicardNot Available
NebiletNot Available
NebilongNot Available
NodonNot Available
NubetaNot Available
Brand mixturesNot Available
Categories
CAS number99200-09-6
WeightAverage: 405.435
Monoisotopic: 405.175164703
Chemical FormulaC22H25F2NO4
InChI KeyInChIKey=KOHIRBRYDXPAMZ-UHFFFAOYSA-N
InChI
InChI=1S/C22H25F2NO4/c23-15-3-7-19-13(9-15)1-5-21(28-19)17(26)11-25-12-18(27)22-6-2-14-10-16(24)4-8-20(14)29-22/h3-4,7-10,17-18,21-22,25-27H,1-2,5-6,11-12H2
IUPAC Name
1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-{[2-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-hydroxyethyl]amino}ethan-1-ol
SMILES
OC(CNCC(O)C1CCC2=C(O1)C=CC(F)=C2)C1CCC2=C(O1)C=CC(F)=C2
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzopyrans
SubclassNot Available
Direct parentBenzopyrans
Alternative parentsFluorobenzenes; Alkyl Aryl Ethers; Aryl Fluorides; Secondary Alcohols; 1,2-Aminoalcohols; Dialkylamines; Polyamines; Organofluorides
Substituentsfluorobenzene; alkyl aryl ether; aryl fluoride; benzene; aryl halide; 1,2-aminoalcohol; secondary alcohol; polyamine; ether; secondary aliphatic amine; secondary amine; organofluoride; amine; organohalogen; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the benzopyrans. These are organic compounds containing a benzene ring fused to a pyran ring.
Pharmacology
IndicationFor the treatment of essential hypertension.
PharmacodynamicsNebivolol is a competitive and highly selective beta-1 receptor antagonist with mild vasodilating properties, possibly due to an interaction with the L-arginine/nitric oxide pathway. In preclinical studies, nebivolol has been shown to induce endothelium-dependent arterial relaxation in a dose dependent manner, by stimulation of the release of endothelial nitric oxide. Nitric oxide acts to relax vascular smooth muscle cells and inhibits platelet aggregation and adhesion.
Mechanism of actionNebivolol is a selective β1-receptor antagonist. Activation of β1-receptors by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Nebivolol blocks these receptors which reverses the effects of epinephrine, lowering the heart rate and blood pressure. In addition, beta blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels. At high enough concentrations, this drug may also bind beta 2 receptors.
AbsorptionThe absorption of nebivolol is rapid and not affected by food.
Volume of distributionNot Available
Protein binding98%
Metabolism

Hepatic (CYP2D6-mediated)

Route of eliminationNot Available
Half life10 hours
ClearanceNot Available
ToxicityThe most common signs and symptoms associated with nebivolol overdosage are bradycardia and hypotension. Other important adverse events reported with nebivolol overdose include cardiac failure, dizziness, hypoglycemia, fatigue and vomiting. Other adverse events associated with β-blocker overdose include bronchospasm and heart block. The largest known ingestion of nebivolol worldwide involved a patient who ingested up to 500 mg of nebivolol along with several 100 mg tablets of acetylsalicylic acid in a suicide attempt. The patient experienced hyperhydrosis, pallor, depressed level of consciousness, hypokinesia, hypotension, sinus bradycardia, hypoglycemia, hypokalemia, respiratory failure and vomiting. The patient recovered.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Nebivolol Action PathwayDrug actionSMP00366
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8483
Blood Brain Barrier + 0.7802
Caco-2 permeable - 0.5549
P-glycoprotein substrate Substrate 0.7928
P-glycoprotein inhibitor I Non-inhibitor 0.7443
P-glycoprotein inhibitor II Non-inhibitor 0.567
Renal organic cation transporter Non-inhibitor 0.8016
CYP450 2C9 substrate Non-substrate 0.8738
CYP450 2D6 substrate Non-substrate 0.7248
CYP450 3A4 substrate Non-substrate 0.6822
CYP450 1A2 substrate Inhibitor 0.5145
CYP450 2C9 substrate Non-inhibitor 0.7876
CYP450 2D6 substrate Non-inhibitor 0.5994
CYP450 2C19 substrate Non-inhibitor 0.5923
CYP450 3A4 substrate Non-inhibitor 0.9441
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8336
Ames test Non AMES toxic 0.7132
Carcinogenicity Non-carcinogens 0.9402
Biodegradation Not ready biodegradable 0.9953
Rat acute toxicity 2.7228 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.5769
hERG inhibition (predictor II) Inhibitor 0.8381
Pharmacoeconomics
Manufacturers
  • Forest laboratories inc
Packagers
Dosage forms
FormRouteStrength
TabletOral10 mg
TabletOral2.5 mg
TabletOral5 mg
Prices
Unit descriptionCostUnit
Bystolic 10 mg tablet2.09USDtablet
Bystolic 20 mg tablet2.09USDtablet
Bystolic 2.5 mg tablet2.06USDtablet
Bystolic 5 mg tablet2.06USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States65450402000-04-082020-04-08
United States57595801995-06-022015-06-02
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility4.03e-02 g/lALOGPS
logP2.44ALOGPS
logP3.21ChemAxon
logS-4ALOGPS
pKa (strongest acidic)13.52ChemAxon
pKa (strongest basic)8.9ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count3ChemAxon
polar surface area70.95ChemAxon
rotatable bond count6ChemAxon
refractivity103.32ChemAxon
polarizability41.98ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Thomas Bader, Alfred Stutz, Harald Hofmeier, Hans-Ulrich Bichsel, “Process for preparation of racemic Nebivolol.” U.S. Patent US20070149612, issued June 28, 2007.

US20070149612
General Reference
  1. Gielen W, Cleophas TJ, Agrawal R: Nebivolol: a review of its clinical and pharmacological characteristics. Int J Clin Pharmacol Ther. 2006 Aug;44(8):344-57. Pubmed
External Links
ResourceLink
KEGG DrugD05127
PubChem Compound71301
PubChem Substance99443225
ChemSpider64421
Therapeutic Targets DatabaseDAP000942
PharmGKBPA151958426
RxListhttp://www.rxlist.com/bystolic-tablets-drug.htm
Drugs.comhttp://www.drugs.com/cdi/nebivolol.html
PDRhealthhttp://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=bys1940.html&contentName=Bystolic&contentId=732
WikipediaNebivolol
ATC CodesC07AB12
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(69.1 KB)
Interactions
Drug Interactions
Drug
TerazosinIncreased risk of hypotension. Initiate concomitant therapy cautiously.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food InteractionsNot Available

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. Gielen W, Cleophas TJ, Agrawal R: Nebivolol: a review of its clinical and pharmacological characteristics. Int J Clin Pharmacol Ther. 2006 Aug;44(8):344-57. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. de Boer RA, Voors AA, van Veldhuisen DJ: Nebivolol: third-generation beta-blockade. Expert Opin Pharmacother. 2007 Jul;8(10):1539-50. Pubmed

2. Beta-2 adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Beta-2 adrenergic receptor P07550 Details

References:

  1. Nuttall SL, Routledge HC, Kendall MJ: A comparison of the beta1-selectivity of three beta1-selective beta-blockers. J Clin Pharm Ther. 2003 Jun;28(3):179-86. Pubmed

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
Drug created on October 19, 2007 15:00 / Updated on September 16, 2013 17:26