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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H25F2NO4
Molecular Weight 405.435
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEVONEBIVOLOL

SMILES

O[C@@H](CNC[C@H](O)[C@@H]1CCC2=CC(F)=CC=C2O1)[C@H]3CCC4=CC(F)=CC=C4O3

InChI

InChIKey=KOHIRBRYDXPAMZ-YHDSQAASSA-N
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/t17-,18-,21-,22+/m0/s1

HIDE SMILES / InChI
Molecular Formula C22H25F2NO4
Molecular Weight 405.435
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Marketed under the brand name BYSTOLIC, Nebivolol is indicated for the treatment of hypertension, to lower blood pressure. Nebivolol is a racemic mixture containing equal amounts of two enantiomers, d-nebivolol and l-nebivolol (Levonebivolol). It is a selective β1-adrenergic antagonist with vasodilating properties. The d-enantiomer provides selective β1-adrenergic receptor blockade, whereas l-nebivolol possesses vasodilating properties thought to be attributable to nitric oxide modulation via the L-argininenitric oxide pathway. dl-nebivolol exerts an antithrombotic activity by stimulating the formation of NO by platelets, and that this effect is generated by its l-enantiomer, whereas the d-enantiomer exerts a weak antiplatelet effect because of β-adrenergic receptor-independent stimulation of adenyly cyclase. L-nebivolol had a protective effect against both endothelial dysfunction of the mesenteric artery and ileal injury induced by intestinal I/R; however, similar effects were not observed for racemic nebivolol. d-Nebivolol (SRRR) and nebivolol showed combined high affinity and selectivity for inhibition of beta 1-adrenergic receptor coupled accumulation of cAMP in CHO-Hu beta 1 cells (0.41 and 0.42 nM for d-nebivolol and nebivolol, respectively). l-Nebivolol (RSSS) was 1460 times less potent than d-nebivolol in CHO-Hu beta 1 cells.

CNS Activity

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2752
Modulator
846
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
BYSTOLIC

Approved Use

BYSTOLIC is a beta-adrenergic blocking agent indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. BYSTOLIC may be used alone or in combination with other antihypertensive agents .

Launch Date

2007
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.31 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26914703/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1.98 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26914703/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1.38 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26914703/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.5 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/24141040/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6.83 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26914703/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9.94 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26914703/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
6.41 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26914703/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9.4 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/24141040/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
48 μg × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9112066/
0.073 mg/kg single, intravenous
dose: 0.073 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
36.7 μg × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9112066/
0.073 mg/kg single, intravenous
dose: 0.073 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.79 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26914703/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
12.43 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26914703/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
12.87 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26914703/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
14.5 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/24141040/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
12.1 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9112066/
0.073 mg/kg single, intravenous
dose: 0.073 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
11.3 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9112066/
0.073 mg/kg single, intravenous
dose: 0.073 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
LEVONEBIVOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
REVIEW
https://pubmed.ncbi.nlm.nih.gov/9990650/
LEVONEBIVOLOL plasma
Homo sapiens
PubMed

PubMed

TitleDatePubMed
Nebivolol has protective effect against endothelial and ileal dysfunction due to I/R.
2011-03
Different pharmacological properties of two enantiomers in a unique beta-blocker, nebivolol.
2008
Effect of DL-nebivolol, its enantiomers and metabolites on the intracellular production of superoxide and nitric oxide in human endothelial cells.
2007-04
Nebivolol: a novel beta-blocker with nitric oxide-induced vasodilatation.
2006
Patents

Patents

20100076206
1
8003810
1

Sample Use Guides

In Vivo Use Guide
The effects of racemic nebivolol, 2.5, 5.0, and 10.0 mg; d-nebivolol, 2.5 mg; l-nebivolol, 2.5 mg; atenolol, 50 mg; and placebo, each given once daily for 7 days, on exercise-induced increases in heart rate and systolic blood pressure were compared in a seven-way double-blind randomized crossover trial in 14 healthy male volunteers.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: D-nebivolol (0.1-10 uM/L), but not L-nebivolol (0.1-10 uM/L), significantly shifted to the right the concentration-response curve to phenylephrine, an alpha(1)-adrenoceptor agonist, in a concentration-dependent manner. https://www.ncbi.nlm.nih.gov/pubmed/19210511
In the isolated guinea pig heart coronary vasodilator potency of L- and D-nebivolol and a possible role of beta2, beta3 adrenoceptors and 5-HT1A receptors in nebivolol-induced vasodilation was analysed. Not only L-nebivolol (3-30 x 10(-6) M) but also D-nebivolol (3-30 x 10(-6) M) induced coronary vasodilation, and both responses were inhibited by L-NAME (10(-4) M).
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:46:25 GMT 2025
Edited
by admin
on Mon Mar 31 18:46:25 GMT 2025
Record UNII
GMK2E335DQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LEVONEBIVOLOL
INN   WHO-DD  
INN  
Official Name English
R-67145
Preferred Name English
R67145
Code English
L-NEBIVOLOL
Common Name English
(1S)-2-(((2S)-2-((2R)-6-FLUORO-3,4-DIHYDRO-2H-CHROMEN-2-YL)-2-HYDROXYETHYL)AMINO)-1-((2S)-6-FLUORO-3,4-DIHYDRO-2H-CHROMEN-2-YL)ETHANOL
Systematic Name English
Levonebivolol [WHO-DD]
Common Name English
(-)-NEBIVOLOL
Common Name English
levonebivolol [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29576
Created by admin on Mon Mar 31 18:46:25 GMT 2025 , Edited by admin on Mon Mar 31 18:46:25 GMT 2025
Code System Code Type Description
CAS
118457-16-2
Created by admin on Mon Mar 31 18:46:25 GMT 2025 , Edited by admin on Mon Mar 31 18:46:25 GMT 2025
PRIMARY
FDA UNII
GMK2E335DQ
Created by admin on Mon Mar 31 18:46:25 GMT 2025 , Edited by admin on Mon Mar 31 18:46:25 GMT 2025
PRIMARY
SMS_ID
300000034355
Created by admin on Mon Mar 31 18:46:25 GMT 2025 , Edited by admin on Mon Mar 31 18:46:25 GMT 2025
PRIMARY
CHEBI
64020
Created by admin on Mon Mar 31 18:46:25 GMT 2025 , Edited by admin on Mon Mar 31 18:46:25 GMT 2025
PRIMARY
INN
8937
Created by admin on Mon Mar 31 18:46:25 GMT 2025 , Edited by admin on Mon Mar 31 18:46:25 GMT 2025
PRIMARY
PUBCHEM
9844194
Created by admin on Mon Mar 31 18:46:25 GMT 2025 , Edited by admin on Mon Mar 31 18:46:25 GMT 2025
PRIMARY
NCI_THESAURUS
C91033
Created by admin on Mon Mar 31 18:46:25 GMT 2025 , Edited by admin on Mon Mar 31 18:46:25 GMT 2025
PRIMARY
Related Record Type Details
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Related Record Type Details
Structure of LEVONEBIVOLOL
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC IN THE EM POPULATION

Tmax PHARMACOKINETIC
blood-to-plasma ratio PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC IN THE PM POPULATION

NIH
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