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Identification
Name Nebivolol
Accession Number DB04861
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Nebivololum [latin]
Salts Not Available
Brand names
Name Company
Bystolic
Lobivon
Nebicard-5
Nebilet
Nebilong
Nebipill
Nodon
Nubeta
PI-21858
Brand mixtures Not Available
Categories
  • Antihypertensive Agents
  • Adrenergic beta-Antagonists
  • Vasodilator Agents
CAS number 99200-09-6
Weight Average: 405.435
Monoisotopic: 405.175164703
Chemical Formula C22H25F2NO4
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzopyrans
Substructures
  • Hydroxy Compounds
  • Pyrans
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Amino Alcohols
  • Benzopyrans
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Alcohols and Polyols
  • Aryl Halides
  • Phenyl Esters
Pharmacology
Indication For the treatment of essential hypertension.
Pharmacodynamics Nebivolol 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 action Nebivolol 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.
Absorption The absorption of nebivolol is rapid and not affected by food.
Volume of distribution Not Available
Protein binding 98%
Metabolism Hepatic (CYP2D6-mediated)
Route of elimination Not Available
Half life 10 hours
Clearance Not Available
Toxicity The 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
Pathway Name SMPDB ID
Smp00366 Nebivolol Pathway SMP00366
Pharmacoeconomics
Manufacturers
  • Forest laboratories inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral 10 mg
Tablet Oral 2.5 mg
Tablet Oral 5 mg
Prices
Unit description Cost Unit
Bystolic 10 mg tablet 2.09 USD tablet
Bystolic 20 mg tablet 2.09 USD tablet
Bystolic 2.5 mg tablet 2.06 USD tablet
Bystolic 5 mg tablet 2.06 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6545040 2000-04-08 2020-04-08
United States 5759580 1995-06-02 2015-06-02
Properties
State solid
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 4.03e-02 g/l ALOGPS
logP 2.44 ALOGPS
logP 3.21 ChemAxon
logS -4 ALOGPS
pKa (strongest acidic) 13.52 ChemAxon
pKa (strongest basic) 8.9 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 70.95 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 103.32 ChemAxon
polarizability 41.98 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D05127 Link_out
PubChem Compound 71301 Link_out
PubChem Substance 99443225 Link_out
ChemSpider 64421 Link_out
Therapeutic Targets Database DAP000942 Link_out
PharmGKB PA151958426 Link_out
RxList http://www.rxlist.com/bystolic-tablets-drug.htm Link_out
Drugs.com http://www.drugs.com/cdi/nebivolol.html Link_out
PDRhealth http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=bys1940.html&contentName=Bystolic&contentId=732 Link_out
Wikipedia http://en.wikipedia.org/wiki/Nebivolol Link_out
ATC Codes
  • C07AB12
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (69.1 KB)
Interactions
Drug Interactions
Drug Interaction
Terazosin Increased risk of hypotension. Initiate concomitant therapy cautiously.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food Interactions Not Available
Targets

1. Beta-1 adrenergic receptor

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: P08588 Link_out
Gene: ADRB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: antagonist

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

Organism class: human
UniProt ID: P07550 Link_out
Gene: ADRB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 February 08, 2013 16:23