You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
1,1'-[Bis(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)]-2,2'-iminodiethanolNot AvailableNot Available
1,1'-Bis(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2,2'-iminodiethanolNot AvailableNot Available
alpha,Alpha'-(iminobismethylene)bis-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol)Not AvailableNot Available
alpha,Alpha'-(iminodimethylene)bis-(6-fluoro-2-chromanmethanol)Not AvailableNot Available
NebivololumLatinNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bystolictablet2.5 mgoralForest Laboratories, Inc.2008-01-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Bystolictablet5 mgoralForest Laboratories, Inc.2008-01-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Bystolictablet10 mgoralForest Laboratories, Inc.2008-01-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Bystolictablet20 mgoralForest Laboratories, Inc.2008-01-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Bystolictablet5 mgoralPhysicians Total Care, Inc.2008-10-02Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Bystolictablet10 mgoralPhysicians Total Care, Inc.2009-04-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Bystolictablet5 mgoralCardinal Health2008-01-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Bystolictablet20 mgoralCardinal Health2008-01-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Bystolictablet10 mgoralCardinal Health2008-01-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Bystolictablet2.5 mgoralForest Laboratories Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Bystolictablet5.0 mgoralForest Laboratories Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Bystolictablet10.0 mgoralForest Laboratories Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Bystolictablet20.0 mgoralForest Laboratories Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
LobivonNot Available
NebicardNot Available
NebiletNot Available
NebilongNot Available
NodonNot Available
NubetaNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Nebivolol hydrochloride
ThumbNot applicableDBSALT001027
Categories
CAS number99200-09-6
WeightAverage: 405.435
Monoisotopic: 405.175164703
Chemical FormulaC22H25F2NO4
InChI KeyKOHIRBRYDXPAMZ-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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 1-benzopyrans. These are organic aromatic compounds that 1-benzopyran, a bicyclic compound made up of a benzene ring fused to a pyran, so that the oxygen atom is at the 1-position.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzopyrans
Sub Class1-benzopyrans
Direct Parent1-benzopyrans
Alternative Parents
Substituents
  • 1-benzopyran
  • Aralkylamine
  • Fluorobenzene
  • Alkyl aryl ether
  • Benzenoid
  • Aryl halide
  • Aryl fluoride
  • Secondary alcohol
  • 1,2-aminoalcohol
  • Oxacycle
  • Secondary amine
  • Ether
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
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
PropertyValueProbability
Human Intestinal Absorption+0.8483
Blood Brain Barrier+0.7802
Caco-2 permeable-0.5549
P-glycoprotein substrateSubstrate0.7928
P-glycoprotein inhibitor INon-inhibitor0.7443
P-glycoprotein inhibitor IINon-inhibitor0.567
Renal organic cation transporterNon-inhibitor0.8016
CYP450 2C9 substrateNon-substrate0.8738
CYP450 2D6 substrateNon-substrate0.7248
CYP450 3A4 substrateNon-substrate0.6822
CYP450 1A2 substrateInhibitor0.5145
CYP450 2C9 substrateNon-inhibitor0.7876
CYP450 2D6 substrateNon-inhibitor0.5994
CYP450 2C19 substrateNon-inhibitor0.5923
CYP450 3A4 substrateNon-inhibitor0.9441
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8336
Ames testNon AMES toxic0.7132
CarcinogenicityNon-carcinogens0.9402
BiodegradationNot ready biodegradable0.9953
Rat acute toxicity2.7228 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5769
hERG inhibition (predictor II)Inhibitor0.8381
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral10 mg
Tabletoral10.0 mg
Tabletoral2.5 mg
Tabletoral20 mg
Tabletoral20.0 mg
Tabletoral5 mg
Tabletoral5.0 mg
Prices
Unit descriptionCostUnit
Bystolic 10 mg tablet2.09USD tablet
Bystolic 20 mg tablet2.09USD tablet
Bystolic 2.5 mg tablet2.06USD tablet
Bystolic 5 mg tablet2.06USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States57595801995-06-022015-06-02
United States65450402000-04-082020-04-08
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0403 mg/mLALOGPS
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 Area70.95 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity103.32 m3·mol-1ChemAxon
Polarizability41.98 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
ATC CodesC07AB12
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (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

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. 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

Enzymes

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
comments powered by Disqus
Drug created on October 19, 2007 15:00 / Updated on September 16, 2013 17:26