Nebivolol

Identification

Summary

Nebivolol is a beta blocking agent used to treat hypertension and aid in the management of heart failure.

Brand Names
Bystolic
Generic Name
Nebivolol
DrugBank Accession Number
DB04861
Background

Nebivolol is a racemic mixture of 2 enantiomers where one is a beta adrenergic antagonist and the other acts as a cardiac stimulant without beta adrenergic activity.2 Treatment with nebivolol leads to a greater decrease in systolic and diastolic blood pressure than atenolol, propranolol, or pindolol.2 Nebivolol and other beta blockers are generally not first line therapies as many patients are first treated with thiazide diuretics.[A182594]

Nebivolol was granted FDA approval on 17 December 2007.8

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 405.435
Monoisotopic: 405.175164703
Chemical Formula
C22H25F2NO4
Synonyms
  • Narbivolol
  • Nebivolol
  • Nebivololum
External IDs
  • PI-21858
  • R-65824
  • R65,824

Pharmacology

Indication

Nebivolol is indicated to treat hypertension.1,2,8,9

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Nebivolol is a selective beta-1 adrenergic receptor antagonist that decreases vascular resistance, increases stroke volume and cardiac output, and does not negatively affect left ventricular function.2,3 It has a long duration of action as effects can be seen 48 hours after stopping the medication and a wide therapeutic window as patients generally take 5-40mg daily.2,8 Patients should not abruptly stop taking this medication as this may lead to exacerbation of coronary artery disease.8 Diabetic patients should monitor their blood glucose levels as beta blockers may mask signs of hypoglycemia.8

Mechanism of action

Nebivolol is a highly selective beta-1 adrenergic receptor antagonist2 with weak beta-2 adrenergic receptor antagonist activity.3 Blocking beta-1 adrenergic receptors by d-nebivolol leads to decreased resting heart rate, exercise heart rate, myocardial contracility, systolic blood pressure, and diastolic blood pressure.4,2,3,5 The selectivity of d-nebivolol limits the magnitude of beta blocker adverse effects in the airways or relating to insulin sensitivity.5 Nebivolol also inhibits aldosterone, and beta-1 antagonism in the juxtaglomerular apparatus also inhibits the release of renin.5 Decreased aldosterone leads to decreased blood volume, and decreased renin leads to reduced vasoconstriction.5 l-nebivolol is responsible for beta-3 adrenergic receptor agonist activity that stimulates endothelial nitric oxide synthase, increasing nitric oxide levels; leading to vasodilation, decreased peripheral vascular resistance, increased stroke volume, ejection fraction, and cardiac output.1,4,2,3,5 The vasodilation, reduced oxidative stress, and reduced platelet volume and aggregation of nebivolol may lead to benefits in heart failure patients.4

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Humans
UBeta-2 adrenergic receptor
antagonist
Humans
UBeta-3 adrenergic receptor
agonist
Humans
Absorption

The absorption of nebivolol is not affected by food.8 Nebivolol has a Tmax of 1.5-4 hours.8 Bioavailability can range from 12-96% for extensive to poor CYP2D6 metabolizers.6,7 For a 20mg dose, d-nebivolol has a Cmax of 2.75±1.55ng/mL, l-nebivolol has a Cmax of 5.29±2.06ng/mL, both enantiomers have a Cmax of 8.02±3.47ng/mL, and nebivolol glucuronides have a Cmax of 68.34±44.68ng/mL.6 For a 20mg dose, d-nebivolol has an AUC of 13.78±15.27ng*h/mL, l-nebivolol has an AUC of 27.72±15.32ng*h/mL, both enantiomers have an AUC of 41.50±29.76ng*h/mL, and nebivolol glucuronides have an AUC of 396.78±297.94ng*h/mL.6

Volume of distribution

For a 20mg dose, d-nebivolol has an apparent volume of distribution of 10,290.81±3911.72L, l-nebivolol has an apparent volume of distribution of 8,066.66±4,055.50L, and both enantiomers together have a volume of distribution of 10,423.42±6796.50L.6

Protein binding

Nebivolol is 98% bound to plasma proteins, mostly to serum albumin.8

Metabolism

Nebivolol is metabolized mainly by glucuronidation and CYP2D6 mediated hydroxylation.1,4 Metabolism involves n-dealkylation, hydroxylation, oxidation, and glucuronidation.7 Aromatic hydroxyl and acyclic oxide metabolites are active, while n-dealkylated and glucuronides are inactive.7

Hover over products below to view reaction partners

Route of elimination

In extensive CYP2D6 metabolizers, 38% is eliminated in the urine and 44% in the feces.8 In poor CYP2D6 metabolizers, 67% is eliminated in the urine and 13% in the feces.8 <1% of a dose is excreted as the unmetabolized drug.5

Half-life

d-nebivolol has a half life of 12 hours in CYP2D6 extensive metabolizers and 19 hours in poor metabolizers.5,8

Clearance

For a 20mg dose, the clearance of d-nebivolol is 1241.63±749.77L/h, l-nebivolol is 435.53±180.93L/h, and both enantiomers is 635.31±300.25L/h.6

Adverse Effects
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Toxicity

Patients experiencing an overdose may present with bradycardia, hypotension, cardiac failure, dizziness, hypoglycemia, fatigue, vomiting, bronchospasm and heart block.8 Treat overdose with general supportive measures including intravenous atropine for bradycardia, vasopressors and intravenous fluids for hypotension, isoproterenol infusion for heart block, digitalis glycosides and diuretics for congestive heart failure, bronchodilators for bronchospasm, and intravenous glucose for hypoglycemia.8

Pathways
PathwayCategory
Nebivolol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Nebivolol can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Nebivolol can be increased when combined with Abatacept.
AbirateroneThe metabolism of Nebivolol can be decreased when combined with Abiraterone.
AcarboseThe therapeutic efficacy of Acarbose can be increased when used in combination with Nebivolol.
AcebutololAcebutolol may increase the arrhythmogenic activities of Nebivolol.
AceclofenacAceclofenac may decrease the antihypertensive activities of Nebivolol.
AcemetacinAcemetacin may decrease the antihypertensive activities of Nebivolol.
AcenocoumarolThe metabolism of Nebivolol can be decreased when combined with Acenocoumarol.
AcetaminophenThe metabolism of Nebivolol can be decreased when combined with Acetaminophen.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be increased when used in combination with Nebivolol.
Interactions
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Food Interactions
  • Avoid alcohol.
  • Take with or without food.

Products

Products
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Product Ingredients
IngredientUNIICASInChI Key
Nebivolol hydrochlorideJGS34J7L9I152520-56-4JWEXHQAEWHKGCW-VCVZPGOSSA-N
Product Images
International/Other Brands
Lobivon / Nebicard / Nebilet / Nebilong / Nodon / Nubeta
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BystolicTablet5 mg/1OralCardinal Health2008-01-22Not applicableUS flag55154 462120180913 8702 15cf2gv
BystolicTablet5 mgOralAllergan2013-04-02Not applicableCanada flag
BystolicTablet20 mg/1OralMed Pharma Co., Ltd.2011-06-012012-06-21US flag
BystolicTablet5 mg/1OralA-S Medication Solutions2008-01-222016-09-27US flag50090 112720180913 8702 fyvf8e
BystolicTablet20 mg/1OralAllergan, Inc.2008-01-22Not applicableUS flag0456 142020180907 15195 ct9a84
BystolicTablet10 mg/1OralPhysicians Total Care, Inc.2009-04-15Not applicableUS flag54868 601820180907 15195 6adn2a
BystolicTablet20 mg/1OralCardinal Health2008-01-22Not applicableUS flag00456 1420 30 nlmimage10 44132249
BystolicTablet5 mg/1OralA-S Medication Solutions2008-01-22Not applicableUS flag54569 611920180907 15195 cxsndv
BystolicTablet10 mg/1OralA-S Medication Solutions2008-01-22Not applicableUS flag50090 130720180913 8702 3ph42
BystolicTablet20 mgOralAllergan2013-04-02Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-nebivololTablet2.5 mgOralApotex CorporationNot applicableNot applicableCanada flag
Apo-nebivololTablet20 mgOralApotex CorporationNot applicableNot applicableCanada flag
Apo-nebivololTablet5 mgOralApotex CorporationNot applicableNot applicableCanada flag
NebivololTablet5 mg/1OralTorrent Pharmaceuticals Limited2018-03-02Not applicableUS flag
NebivololTablet5 mg/1OralAmerigen Pharmaceuticals Inc.2015-04-28Not applicableUS flag
NebivololTablet20 mg/1OralTorrent Pharmaceuticals Limited2018-03-02Not applicableUS flag
NebivololTablet2.5 mg/1OralTorrent Pharmaceuticals Limited2018-03-02Not applicableUS flag
NebivololTablet20 mg/1OralAmerigen Pharmaceuticals Inc.2015-04-28Not applicableUS flag
NebivololTablet2.5 mg/1OralAmerigen Pharmaceuticals Inc.2015-04-28Not applicableUS flag
NebivololTablet10 mg/1OralTorrent Pharmaceuticals Limited2018-03-02Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AMLONEB 10 MG/10 MG TABLET, 30 ADETNebivolol hydrochloride (10 mg) + Amlodipine besylate (10 mg)TabletOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
AMLONEB 10 MG/10 MG TABLET, 90 ADETNebivolol hydrochloride (10 mg) + Amlodipine besylate (10 mg)TabletOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
AMLONEB 10 MG/2.5 MG TABLET, 30 ADETNebivolol hydrochloride (2.5 mg) + Amlodipine besylate (10 mg)TabletOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
AMLONEB 10 MG/2.5 MG TABLET, 90 ADETNebivolol hydrochloride (2.5 mg) + Amlodipine besylate (10 mg)TabletOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
AMLONEB 10 MG/5 MG TABLET, 30 ADETNebivolol hydrochloride (5 mg) + Amlodipine besylate (10 mg)TabletOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
AMLONEB 10 MG/5 MG TABLET, 90 ADETNebivolol hydrochloride (5 mg) + Amlodipine besylate (10 mg)TabletOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
AMLONEB 5 MG/10 MG TABLET, 30 ADETNebivolol hydrochloride (10 mg) + Amlodipine besylate (5 mg)TabletOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
AMLONEB 5 MG/10 MG TABLET, 90 ADETNebivolol hydrochloride (10 mg) + Amlodipine besylate (5 mg)TabletOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
AMLONEB 5 MG/2.5 MG TABLET, 30 ADETNebivolol hydrochloride (2.5 mg) + Amlodipine besylate (5 mg)TabletOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
AMLONEB 5 MG/2.5 MG TABLET, 90 ADETNebivolol hydrochloride (2.5 mg) + Amlodipine besylate (5 mg)TabletOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag

Categories

ATC Codes
C07FB12 — Nebivolol and amlodipineC09DX05 — Valsartan and nebivololC07BB12 — Nebivolol and thiazidesC07AB12 — Nebivolol
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzopyrans
Sub Class
1-benzopyrans
Direct Parent
1-benzopyrans
Alternative Parents
Aralkylamines / Alkyl aryl ethers / Benzenoids / Aryl fluorides / Secondary alcohols / 1,2-aminoalcohols / Oxacyclic compounds / Dialkylamines / Organopnictogen compounds / Organofluorides
show 1 more
Substituents
1,2-aminoalcohol / 1-benzopyran / Alcohol / Alkyl aryl ether / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Benzenoid
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, secondary alcohol, secondary amino compound, diol, chromanes (CHEBI:64019)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
030Y90569U
CAS number
118457-14-0
InChI Key
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

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. [Article]
  2. De Cree J, Cobo C, Geukens H, Verhaegen H: Comparison of the subacute hemodynamic effects of atenolol, propranolol, pindolol, and nebivolol. Angiology. 1990 Feb;41(2):95-105. doi: 10.1177/000331979004100202. [Article]
  3. Van de Water A, Janssens W, Van Neuten J, Xhonneux R, De Cree J, Verhaegen H, Reneman RS, Janssen PA: Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist. J Cardiovasc Pharmacol. 1988 May;11(5):552-63. doi: 10.1097/00005344-198805000-00007. [Article]
  4. Fongemie J, Felix-Getzik E: A Review of Nebivolol Pharmacology and Clinical Evidence. Drugs. 2015 Aug;75(12):1349-71. doi: 10.1007/s40265-015-0435-5. [Article]
  5. Giles TD, Cockcroft JR, Pitt B, Jakate A, Wright HM: Rationale for nebivolol/valsartan combination for hypertension: review of preclinical and clinical data. J Hypertens. 2017 Sep;35(9):1758-1767. doi: 10.1097/HJH.0000000000001412. [Article]
  6. Chen CL, Desai-Krieger D, Ortiz S, Kerolous M, Wright HM, Ghahramani P: A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the Pharmacokinetic and Pharmacodynamic Interaction Between Nebivolol and Valsartan in Healthy Volunteers at Steady State. Am J Ther. 2015 Sep-Oct;22(5):e130-40. doi: 10.1097/MJT.0000000000000247. [Article]
  7. Briciu C, Neag M, Muntean D, Bocsan C, Buzoianu A, Antonescu O, Gheldiu AM, Achim M, Popa A, Vlase L: Phenotypic differences in nebivolol metabolism and bioavailability in healthy volunteers. Clujul Med. 2015;88(2):208-13. doi: 10.15386/cjmed-395. Epub 2015 Apr 15. [Article]
  8. FDA Approved Drug Products: Nebivolol Tablets [Link]
  9. FDA Approved Drug Products: Nebivolol and Valsartan Tablets [Link]
Human Metabolome Database
HMDB0015594
KEGG Drug
D05127
PubChem Compound
71301
PubChem Substance
99443225
ChemSpider
64421
BindingDB
84735
RxNav
31555
ChEBI
64019
ChEMBL
CHEMBL434394
Therapeutic Targets Database
DAP000942
PharmGKB
PA151958426
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Nebivolol
MSDS
Download (69.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceAortic Blood Pressure1
4CompletedBasic ScienceSyndrome, Metabolic1
4CompletedDiagnosticHigh Blood Pressure (Hypertension)2
4CompletedHealth Services ResearchJNC 7 Stage 1 or 2 Hypertension1
4CompletedOtherHigh Blood Pressure (Hypertension) / Prehypertension2
4CompletedPreventionBlood Pressures / Hypertension Complicated / Left Ventricular Hypertrophy1
4CompletedTreatmentAltitude / Heart Failure / Hypoxia1
4CompletedTreatmentArteriospasm coronary1
4CompletedTreatmentAtherosclerosis / Endothelial Function1
4CompletedTreatmentChronic Heart Failure (CHF)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Forest Laboratories Inc.
  • Forest Pharmaceuticals
  • Mylan
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
TabletOral
TabletOral10 mg/1
TabletOral10 mg
TabletOral2.5 mg/1
TabletOral2.5 mg
TabletOral20 mg
TabletOral20 mg/1
TabletOral5 mg/1
Tablet, film coatedOral
TabletOral
Tablet, film coatedOral
Tablet, coatedOral
Tablet, coated
TabletOral5 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)Region
US5759580No1998-06-022015-06-02US flag
US6545040No2003-04-082021-12-17US flag
US7803838No2010-09-282026-08-29US flag
US7838552No2010-11-232027-10-04US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)223.0-228.0https://www.tcichemicals.com/eshop/en/gb/commodity/N0954/
water solubility0.091g/100mLhttp://www.medicines.org.au/files/txpnebiv.pdf
logP4.183https://www.sigmaaldrich.com/MSDS/MSDS/DisplayMSDSPage.do?country=CA&language=en&productNumber=N1915&brand=SIGMA&PageToGoToURL=https%3A%2F%2Fwww.sigmaaldrich.com%2Fcatalog%2Fproduct%2Fsigma%2Fn1915%3Flang%3Den
pKa8.13http://www.medicines.org.au/files/txpnebiv.pdf
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 RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets
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Kind
Protein
Organism
Humans
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 e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
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. [Article]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  3. de Boer RA, Voors AA, van Veldhuisen DJ: Nebivolol: third-generation beta-blockade. Expert Opin Pharmacother. 2007 Jul;8(10):1539-50. [Article]
Kind
Protein
Organism
Humans
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 ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
Gene Name
ADRB3
Uniprot ID
P13945
Uniprot Name
Beta-3 adrenergic receptor
Molecular Weight
43518.615 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. [Article]
  2. Fongemie J, Felix-Getzik E: A Review of Nebivolol Pharmacology and Clinical Evidence. Drugs. 2015 Aug;75(12):1349-71. doi: 10.1007/s40265-015-0435-5. [Article]
  3. De Cree J, Cobo C, Geukens H, Verhaegen H: Comparison of the subacute hemodynamic effects of atenolol, propranolol, pindolol, and nebivolol. Angiology. 1990 Feb;41(2):95-105. doi: 10.1177/000331979004100202. [Article]
  4. Van de Water A, Janssens W, Van Neuten J, Xhonneux R, De Cree J, Verhaegen H, Reneman RS, Janssen PA: Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist. J Cardiovasc Pharmacol. 1988 May;11(5):552-63. doi: 10.1097/00005344-198805000-00007. [Article]
  5. Giles TD, Cockcroft JR, Pitt B, Jakate A, Wright HM: Rationale for nebivolol/valsartan combination for hypertension: review of preclinical and clinical data. J Hypertens. 2017 Sep;35(9):1758-1767. doi: 10.1097/HJH.0000000000001412. [Article]

Enzymes

Kind
Protein
Organism
Humans
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 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. [Article]
  2. Flockhart Table of Drug Interactions [Link]
  3. FDA Approved Drug Products: Nebivolol Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Hocht C, Bertera FM, Mayer MA, Taira CA: Issues in drug metabolism of major antihypertensive drugs: beta-blockers, calcium channel antagonists and angiotensin receptor blockers. Expert Opin Drug Metab Toxicol. 2010 Feb;6(2):199-211. doi: 10.1517/17425250903397381. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Hu X, Lan T, Dai D, Xu RA, Yuan L, Zhou Q, Li Y, Cai J, Hu G: Evaluation of 24 CYP2D6 Variants on the Metabolism of Nebivolol In Vitro. Drug Metab Dispos. 2016 Nov;44(11):1828-1831. doi: 10.1124/dmd.116.071811. Epub 2016 Aug 18. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: Nebivolol Tablets [Link]

Drug created on October 19, 2007 21:00 / Updated on July 23, 2021 16:03