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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
1,1'-[Bis(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)]-2,2'-iminodiethanol
1,1'-Bis(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2,2'-iminodiethanol
alpha,alpha'-(iminobismethylene)bis-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol)
alpha,alpha'-(iminodimethylene)bis-(6-fluoro-2-chromanmethanol)
Narbivolol
Nebivololum
External Identifiers
  • PI-21858
  • R65,824
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bystolictablet2.5 mg/1oralForest Laboratories, Inc.2008-01-222016-04-23Us
Bystolictablet10 mg/1oralCardinal Health2008-01-222016-04-05Us
Bystolictablet20 mg/1oralCardinal Health2008-01-222016-04-05Us
Bystolictablet5 mg/1oralAvera Mc Kennan Hospital2015-03-192016-04-05Us
Bystolictablet5 mg/1oralCardinal Health2008-01-222016-04-05Us
Bystolictablet20.0 mgoralForest Laboratories Canada Inc2013-04-02Not applicableCanada
Bystolictablet10 mg/1oralPhysicians Total Care, Inc.2009-04-152016-04-05Us
Bystolictablet10.0 mgoralForest Laboratories Canada Inc2013-04-02Not applicableCanada
Bystolictablet5 mg/1oralPhysicians Total Care, Inc.2008-10-022016-04-05Us
Bystolictablet5.0 mgoralForest Laboratories Canada Inc2013-04-02Not applicableCanada
Bystolictablet20 mg/1oralForest Laboratories, Inc.2008-01-222016-04-23Us
Bystolictablet2.5 mgoralForest Laboratories Canada Inc2013-04-02Not applicableCanada
Bystolictablet10 mg/1oralForest Laboratories, Inc.2008-01-222016-04-23Us
Bystolictablet10 mg/1oralCarilion Materials Management2008-01-222016-04-05Us
Bystolictablet5 mg/1oralForest Laboratories, Inc.2008-01-222016-04-23Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nebivololtablet2.5 mg/1oralAmerigen Pharmaceuticals Inc.2015-04-282016-04-05Us
Nebivololtablet20 mg/1oralAmerigen Pharmaceuticals Inc.2015-04-282016-04-05Us
Nebivololtablet10 mg/1oralAmerigen Pharmaceuticals Inc.2015-04-282016-04-05Us
Nebivololtablet5 mg/1oralAmerigen Pharmaceuticals Inc.2015-04-282016-04-05Us
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
152520-56-4
ThumbNot applicableDBSALT001027
Categories
UNII030Y90569U
CAS number118457-14-0
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
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.
Related Articles
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 inhibitorNon-inhibitor0.7876
CYP450 2D6 inhibitorNon-inhibitor0.5994
CYP450 2C19 inhibitorNon-inhibitor0.5923
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral10 mg/1
Tabletoral10.0 mg
Tabletoral2.5 mg/1
Tabletoral2.5 mg
Tabletoral20 mg/1
Tabletoral20.0 mg
Tabletoral5 mg/1
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
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5759580 No1995-06-022015-06-02Us
US6545040 No2001-12-172021-12-17Us
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 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:16961165 ]
External Links
ATC CodesC07AB12C07BB12C07FB12
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (69.1 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Nebivolol can be increased when it is combined with Abiraterone.
AcepromazineAcepromazine may increase the hypotensive activities of Nebivolol.
AcetylcholineThe risk or severity of adverse effects can be increased when Nebivolol is combined with Acetylcholine.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Nebivolol.
AlfuzosinNebivolol may increase the orthostatic hypotensive activities of Alfuzosin.
AmifostineNebivolol may increase the hypotensive activities of Amifostine.
AmiodaroneThe serum concentration of Nebivolol can be increased when it is combined with Amiodarone.
BretyliumBretylium may increase the bradycardic activities of Nebivolol.
BrimonidineBrimonidine may increase the antihypertensive activities of Nebivolol.
BupivacaineThe serum concentration of Bupivacaine can be increased when it is combined with Nebivolol.
BupropionThe serum concentration of Nebivolol can be increased when it is combined with Bupropion.
ButabarbitalThe serum concentration of Nebivolol can be decreased when it is combined with Butabarbital.
ButethalThe serum concentration of Nebivolol can be decreased when it is combined with Butethal.
CabergolineNebivolol may increase the vasoconstricting activities of Cabergoline.
CarbacholThe risk or severity of adverse effects can be increased when Nebivolol is combined with Carbachol.
CelecoxibThe serum concentration of Nebivolol can be increased when it is combined with Celecoxib.
CeritinibNebivolol may increase the bradycardic activities of Ceritinib.
ChloroquineThe serum concentration of Nebivolol can be increased when it is combined with Chloroquine.
ChlorpromazineThe serum concentration of Nebivolol can be increased when it is combined with Chlorpromazine.
ChlorpropamideNebivolol may increase the hypoglycemic activities of Chlorpropamide.
CimetidineThe serum concentration of Nebivolol can be increased when it is combined with Cimetidine.
CinacalcetThe serum concentration of Nebivolol can be increased when it is combined with Cinacalcet.
ClobazamThe serum concentration of Nebivolol can be increased when it is combined with Clobazam.
ClomipramineThe serum concentration of Nebivolol can be increased when it is combined with Clomipramine.
ClozapineThe serum concentration of Nebivolol can be increased when it is combined with Clozapine.
CocaineThe serum concentration of Nebivolol can be increased when it is combined with Cocaine.
DarifenacinThe serum concentration of Nebivolol can be increased when it is combined with Darifenacin.
DelavirdineThe serum concentration of Nebivolol can be increased when it is combined with Delavirdine.
DesipramineThe serum concentration of Nebivolol can be increased when it is combined with Desipramine.
DiazoxideDiazoxide may increase the hypotensive activities of Nebivolol.
DigoxinNebivolol may increase the bradycardic activities of Digoxin.
DiphenhydramineThe serum concentration of Nebivolol can be increased when it is combined with Diphenhydramine.
DipivefrinDipivefrin may increase the atrioventricular blocking (AV block) activities of Nebivolol.
DipyridamoleDipyridamole may increase the bradycardic activities of Nebivolol.
DisopyramideDisopyramide may increase the bradycardic activities of Nebivolol.
DronedaroneDronedarone may increase the bradycardic activities of Nebivolol.
DuloxetineThe serum concentration of Nebivolol can be increased when it is combined with Duloxetine.
EliglustatThe serum concentration of Nebivolol can be increased when it is combined with Eliglustat.
EsmololEsmolol may increase the bradycardic activities of Nebivolol.
FingolimodNebivolol may increase the bradycardic activities of Fingolimod.
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Nebivolol.
FluoxetineThe serum concentration of Nebivolol can be increased when it is combined with Fluoxetine.
HaloperidolThe serum concentration of Nebivolol can be increased when it is combined with Haloperidol.
HeptabarbitalThe serum concentration of Nebivolol can be decreased when it is combined with Heptabarbital.
HexobarbitalThe serum concentration of Nebivolol can be decreased when it is combined with Hexobarbital.
ImipramineThe serum concentration of Nebivolol can be increased when it is combined with Imipramine.
InfliximabInfliximab may decrease the antihypertensive activities of Nebivolol.
IsoniazidThe serum concentration of Nebivolol can be increased when it is combined with Isoniazid.
IvabradineNebivolol may increase the bradycardic activities of Ivabradine.
KetoconazoleThe serum concentration of Nebivolol can be increased when it is combined with Ketoconazole.
LacosamideNebivolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
LevodopaNebivolol may increase the orthostatic hypotensive activities of Levodopa.
LidocaineThe serum concentration of Lidocaine can be increased when it is combined with Nebivolol.
LorcaserinThe serum concentration of Nebivolol can be increased when it is combined with Lorcaserin.
MepivacaineThe serum concentration of Mepivacaine can be increased when it is combined with Nebivolol.
MethacholineThe risk or severity of adverse effects can be increased when Nebivolol is combined with Methacholine.
MethadoneThe serum concentration of Nebivolol can be increased when it is combined with Methadone.
MethohexitalThe serum concentration of Nebivolol can be decreased when it is combined with Methohexital.
MethotrimeprazineThe serum concentration of Nebivolol can be increased when it is combined with Methotrimeprazine.
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Nebivolol.
MidodrineNebivolol may increase the bradycardic activities of Midodrine.
MirabegronThe serum concentration of Nebivolol can be increased when it is combined with Mirabegron.
MolsidomineMolsidomine may increase the hypotensive activities of Nebivolol.
MoxonidineMoxonidine may increase the hypotensive activities of Nebivolol.
NicardipineThe serum concentration of Nebivolol can be increased when it is combined with Nicardipine.
NicorandilNicorandil may increase the hypotensive activities of Nebivolol.
NifedipineNifedipine may increase the hypotensive activities of Nebivolol.
NilotinibThe serum concentration of Nebivolol can be increased when it is combined with Nilotinib.
ObinutuzumabNebivolol may increase the hypotensive activities of Obinutuzumab.
OctreotideOctreotide may increase the bradycardic activities of Nebivolol.
OrciprenalineNebivolol may decrease the activities of Orciprenaline.
PanobinostatThe serum concentration of Nebivolol can be increased when it is combined with Panobinostat.
ParoxetineThe serum concentration of Nebivolol can be increased when it is combined with Paroxetine.
PentobarbitalThe serum concentration of Nebivolol can be decreased when it is combined with Pentobarbital.
PentoxifyllinePentoxifylline may increase the hypotensive activities of Nebivolol.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Nebivolol.
PrazosinNebivolol may increase the orthostatic hypotensive activities of Prazosin.
PrimidoneThe serum concentration of Nebivolol can be decreased when it is combined with Primidone.
PromazineThe serum concentration of Nebivolol can be increased when it is combined with Promazine.
PropafenoneThe serum concentration of Nebivolol can be increased when it is combined with Propafenone.
QuinidineThe serum concentration of Nebivolol can be increased when it is combined with Quinidine.
QuinineThe serum concentration of Nebivolol can be increased when it is combined with Quinine.
RegorafenibRegorafenib may increase the bradycardic activities of Nebivolol.
ReserpineReserpine may increase the hypotensive activities of Nebivolol.
RisperidoneNebivolol may increase the hypotensive activities of Risperidone.
RitonavirThe serum concentration of Nebivolol can be increased when it is combined with Ritonavir.
RituximabNebivolol may increase the hypotensive activities of Rituximab.
RivastigmineRivastigmine may increase the bradycardic activities of Nebivolol.
RolapitantThe serum concentration of Nebivolol can be increased when it is combined with Rolapitant.
RuxolitinibRuxolitinib may increase the bradycardic activities of Nebivolol.
SecobarbitalThe serum concentration of Nebivolol can be decreased when it is combined with Secobarbital.
SertralineThe serum concentration of Nebivolol can be increased when it is combined with Sertraline.
StiripentolThe serum concentration of Nebivolol can be increased when it is combined with Stiripentol.
SufentanilSufentanil may increase the bradycardic activities of Nebivolol.
TacrineTacrine may increase the bradycardic activities of Nebivolol.
TadalafilTadalafil may increase the antihypertensive activities of Nebivolol.
TerbinafineThe serum concentration of Nebivolol can be increased when it is combined with Terbinafine.
TheophyllineNebivolol may decrease the activities of Theophylline.
ThioridazineThe serum concentration of Nebivolol can be increased when it is combined with Thioridazine.
TiclopidineThe serum concentration of Nebivolol can be increased when it is combined with Ticlopidine.
TipranavirThe serum concentration of Nebivolol can be increased when it is combined with Tipranavir.
TofacitinibTofacitinib may increase the bradycardic activities of Nebivolol.
TranylcypromineThe serum concentration of Nebivolol can be increased when it is combined with Tranylcypromine.
TreprostinilTreprostinil may increase the hypotensive activities of Nebivolol.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Nebivolol.
VardenafilVardenafil may increase the antihypertensive activities of Nebivolol.
YohimbineYohimbine may decrease the antihypertensive activities of Nebivolol.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Receptor signaling protein activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular Weight:
51322.1 Da
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:16961165 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  3. de Boer RA, Voors AA, van Veldhuisen DJ: Nebivolol: third-generation beta-blockade. Expert Opin Pharmacother. 2007 Jul;8(10):1539-50. [PubMed:17661735 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Protein homodimerization activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
Gene Name:
ADRB2
Uniprot ID:
P07550
Molecular Weight:
46458.32 Da
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:12795776 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Comments
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Drug created on October 19, 2007 15:00 / Updated on May 02, 2016 02:28