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Details

Stereochemistry RACEMIC
Molecular Formula C22H25F2NO4
Molecular Weight 405.4358
Optical Activity ( + / - )
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NEBIVOLOL

SMILES

C1C[C@]([H])([C@@]([H])(CNC[C@]([H])([C@]2([H])CCc3cc(ccc3O2)F)O)O)Oc4ccc(cc14)F

InChI

InChIKey=KOHIRBRYDXPAMZ-YHBROIRLSA-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+/m1/s1

HIDE SMILES / InChI

Molecular Formula C22H25F2NO4
Molecular Weight 405.4358
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

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. 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. Marketed under the brand name BYSTOLIC, Nebivolol is 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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

1.19784958E12
Primary
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

1.1977632E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.48 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NEBIVOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
7.76 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NEBIVOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NEBIVOLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
unknown
NEBIVOLOL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Co-administed with::
acetylsalicylic acid, oral(>100 mg)
Sources: Page: p.8
healthy
n = 1
Health Status: healthy
Population Size: 1
Sources: Page: p.8
Disc. AE: Hyperhidrosis, Pallor...
AEs leading to
discontinuation/dose reduction:
Hyperhidrosis
Pallor
Depressed level of consciousness
Hypokinesia
Hypotension
Sinus bradycardia
Hypoglycemia
Hypokalemia
Respiratory failure
Vomiting
Sources: Page: p.8
40 mg 1 times / day multiple, oral
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: p.4
unhealthy
n = 6545
Health Status: unhealthy
Condition: Hypertension
Population Size: 6545
Sources: Page: p.4
Disc. AE: Headache, Nausea...
AEs leading to
discontinuation/dose reduction:
Headache (0.4%)
Nausea (0.2%)
Bradycardia (0.2%)
Sources: Page: p.4
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
valsartan, oral(80 mg, qd)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Hypertension
Sources: Page: p.1
Disc. AE: Disorder fetal...
AEs leading to
discontinuation/dose reduction:
Disorder fetal
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Depressed level of consciousness Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Co-administed with::
acetylsalicylic acid, oral(>100 mg)
Sources: Page: p.8
healthy
n = 1
Health Status: healthy
Population Size: 1
Sources: Page: p.8
Hyperhidrosis Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Co-administed with::
acetylsalicylic acid, oral(>100 mg)
Sources: Page: p.8
healthy
n = 1
Health Status: healthy
Population Size: 1
Sources: Page: p.8
Hypoglycemia Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Co-administed with::
acetylsalicylic acid, oral(>100 mg)
Sources: Page: p.8
healthy
n = 1
Health Status: healthy
Population Size: 1
Sources: Page: p.8
Hypokalemia Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Co-administed with::
acetylsalicylic acid, oral(>100 mg)
Sources: Page: p.8
healthy
n = 1
Health Status: healthy
Population Size: 1
Sources: Page: p.8
Hypokinesia Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Co-administed with::
acetylsalicylic acid, oral(>100 mg)
Sources: Page: p.8
healthy
n = 1
Health Status: healthy
Population Size: 1
Sources: Page: p.8
Hypotension Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Co-administed with::
acetylsalicylic acid, oral(>100 mg)
Sources: Page: p.8
healthy
n = 1
Health Status: healthy
Population Size: 1
Sources: Page: p.8
Pallor Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Co-administed with::
acetylsalicylic acid, oral(>100 mg)
Sources: Page: p.8
healthy
n = 1
Health Status: healthy
Population Size: 1
Sources: Page: p.8
Respiratory failure Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Co-administed with::
acetylsalicylic acid, oral(>100 mg)
Sources: Page: p.8
healthy
n = 1
Health Status: healthy
Population Size: 1
Sources: Page: p.8
Sinus bradycardia Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Co-administed with::
acetylsalicylic acid, oral(>100 mg)
Sources: Page: p.8
healthy
n = 1
Health Status: healthy
Population Size: 1
Sources: Page: p.8
Vomiting Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Co-administed with::
acetylsalicylic acid, oral(>100 mg)
Sources: Page: p.8
healthy
n = 1
Health Status: healthy
Population Size: 1
Sources: Page: p.8
Bradycardia 0.2%
Disc. AE
40 mg 1 times / day multiple, oral
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: p.4
unhealthy
n = 6545
Health Status: unhealthy
Condition: Hypertension
Population Size: 6545
Sources: Page: p.4
Nausea 0.2%
Disc. AE
40 mg 1 times / day multiple, oral
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: p.4
unhealthy
n = 6545
Health Status: unhealthy
Condition: Hypertension
Population Size: 6545
Sources: Page: p.4
Headache 0.4%
Disc. AE
40 mg 1 times / day multiple, oral
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: p.4
unhealthy
n = 6545
Health Status: unhealthy
Condition: Hypertension
Population Size: 6545
Sources: Page: p.4
Disorder fetal Disc. AE
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
valsartan, oral(80 mg, qd)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Hypertension
Sources: Page: p.1
Overview

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
minor
yes
yes (co-administration study)
Comment: from product label: fluoxetine coadministration led to increased AUC by 8% and Cmax by 3-fold
Page: 17.0
PubMed

PubMed

TitleDatePubMed
Effects of D-nebivolol and L-nebivolol on left ventricular systolic and diastolic function: comparison with D-L-nebivolol and atenolol.
1993 Aug
Nebivolol: comparison of the effects of dl-nebivolol, d-nebivolol, l-nebivolol, atenolol, and placebo on exercise-induced increases in heart rate and systolic blood pressure.
1998 Sep
[Effect of nebivolol on the level of constitutional, inducible, and total NO-synthase in serum of patients with type II diabetes mellitus].
2002
[Effect of enape combined with nebilet in hypertension].
2002
[Functional and biochemical characteristics of the vasodilator effects of nebivolol in patients with arterial hypertension].
2002
[Assessment of efficacy and safety of nebivolol in patients with stable effort angina].
2002
[Experience of the use of nebivolol in the treatment of hypertension in postmenopausal women].
2002
[Assessment of safety and antihypertensive efficacy of a cardioselective beta-blocker nebivolol in patients with hypertension and concomitant chronic obstructive bronchitis].
2002
[Antihypertensive efficacy and tolerability of nebivolol].
2002
[Autonomic nervous system function and effects of beta-adrenoblockers on heart rhythm variability in patients with myocardial infarction].
2002
[Beta blocker in endothelial dysfunction. Growth of blood vessel cells is halted].
2002 Aug 22
Gateways to clinical trials.
2002 Dec
No-dependent vasodilation induced by nebivolol in coronary circulation is not mediated by beta-adrenoceptors or by 5 HT1A-receptors.
2002 Dec
Effect of nebivolol on left ventricular function in patients with chronic heart failure: a pilot study.
2002 Dec
[Beta blocker enhances NO liberation in the endothelium. Vascular tone long-term improvement].
2002 Dec 5
Nebivolol ameliorates nitric oxide deficient hypertension.
2002 Jun 20
[Despite antihypertensive treatment with beta-blocker patients remain incapacitated].
2002 May 2
Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (SENIORS). Rationale and design.
2002 Nov
[Beta blockade plus NO release. Patients with heart failure can be loaded more].
2002 Oct 10
[Nebivolol effects on platelet aggregation and anticoagulation system].
2003
[Heart rate control with nebivolol in patients with tachysystolic atrial fibrillation].
2003
[The use of nebivolol in menopausal women with hypertension].
2003
[Dynamics of a 24-h profile of arterial pressure and function of the vascular endothelium in nebivolol treatment of hypertensive patients].
2003
[Pharmacological modulation of NO synthesis in patients with arterial hypertension and endothelial dysfunction].
2003
[Effect of nebivolol on the state of pituitary-gonadal system and lipid peroxidation in young and middle aged men with hypertension].
2003
[Clinical and metabolic effects of cardioselective beta-adrenoblockers nebivolol and metoprolol in patients with hypertension and ischemic heart disease associated with type 2 diabetes].
2003
[Use of nebivolol in patients with mild and moderate hypertension].
2003
Angiotensin-converting enzyme inhibition but not beta-adrenergic blockade limits transforming growth factor-beta overexpression in acute normotensive anti-thy1 glomerulonephritis.
2003 Apr
Nebivolol prevents vascular NOS III uncoupling in experimental hyperlipidemia and inhibits NADPH oxidase activity in inflammatory cells.
2003 Apr 1
Involvement of the beta3 adrenoceptor in nebivolol-induced vasorelaxation in the rat aorta.
2003 Aug
Comparison of effects on systolic and diastolic left ventricular function of nebivolol versus atenolol in patients with uncomplicated essential hypertension.
2003 Aug 1
Efficacy and tolerability profile of nebivolol vs atenolol in mild-to-moderate essential hypertension: results of a double-blind randomized multicentre trial.
2003 Dec
[Beta blocker improves the endothelial function. Gas-forming blood vessel protection].
2003 Dec 18
Effect of forced titration of nebivolol on response rate in obese hypertensive patients.
2003 Jan
[Influence of the beta-blocker nebivolol on left ventricular function in patients with chronic heart failure].
2003 Jan 15
The combination of nebivolol plus pravastatin is associated with a more beneficial metabolic profile compared to that of atenolol plus pravastatin in hypertensive patients with dyslipidemia: a pilot study.
2003 Jun
A comparison of the beta1-selectivity of three beta1-selective beta-blockers.
2003 Jun
Different effect of antihypertensive drugs on conduit artery endothelial function.
2003 Jun
Comparison of the new cardioselective beta-blocker nebivolol with bisoprolol in hypertension: the Nebivolol, Bisoprolol Multicenter Study (NEBIS).
2003 May
Evaluation of the efficacy and tolerability of nebivolol versus lisinopril in the treatment of essential arterial hypertension: a randomized, multicentre, double-blind study.
2003 May
Effects of nebivolol on ischemia-induced metabolic changes in dog hearts.
2003 May
[Initial data on nebivolol in heart failure. Beta blockers strengthen older hearts, too].
2003 May 29
Beta-blocker treatment of patients with diastolic heart failure and arterial hypertension. A prospective, randomized, comparison of the long-term effects of atenolol vs. nebivolol.
2003 Oct
[Beta-1 blockade plus NO release. Additional organ protection for patients with hypertension].
2003 Oct 2
[Nebivolol in the treatment of ischemic heart disease patients with chronic heart failure].
2004
The shift in the "paradigm" of the pharmacology of hypertension.
2004
[Genetic polymorphisms in drug metabolizing enzymes--impact on treatment with beta-blockers].
2004 Apr 8
Antioxidant activity of nebivolol in the rat aorta.
2004 Jan
Comparative effects of a two-week treatment with nebivolol and nifedipine in hypertensive patients suffering from COPD.
2004 Mar-Apr
Different pharmacological properties of two enantiomers in a unique beta-blocker, nebivolol.
2008 Summer
Patents

Sample Use Guides

After a 4-week placebo run-in period, 30 patients (mean age 48 years) were randomly allocated to double-blind treatment with either DL-nebivolol 5 mg or D-nebivolol 2.5 mg once daily for 4 weeks.
Route of Administration: Oral
In Vitro Use Guide
Nebivolol and d-nebivolol (SRRR) inhibited noradrenaline-induced cAMP accumulation with IC50 values of 22 and 15 nM, respectively in rat living cardiac cells.
Substance Class Chemical
Created
by admin
on Sat Jun 26 09:33:10 UTC 2021
Edited
by admin
on Sat Jun 26 09:33:10 UTC 2021
Record UNII
030Y90569U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NEBIVOLOL
DASH   INN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
NEBIVOLOL [VANDF]
Common Name English
NEBIVOLOL COMPONENT OF BYVALSON
Common Name English
NEBIVOLOL [INN]
Common Name English
NEBIVOLOL [MI]
Common Name English
NEBIVOLOL [MART.]
Common Name English
NEBIVOLOL [USAN]
Common Name English
R65,824
Code English
NARBIVOLOL
Common Name English
BYVALSON COMPONENT OF NEBIVOLOL
Common Name English
R-65824
Code English
2H-1-BENZOPYRAN-2-METHANOL, .ALPHA.,.ALPHA.'-(IMINOBIS(METHYLENE))BIS(6-FLUORO-3,4-DIHYDRO-, (.ALPHA.R,.ALPHA.'R,2R,2'S)-REL-
Common Name English
.ALPHA.,.ALPHA.'-(IMINODIMETHYLENE)BIS(6-FLUORO-2-CHROMANMETHANOL)
Systematic Name English
NEBIVOLOL [WHO-DD]
Common Name English
Classification Tree Code System Code
LIVERTOX 672
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
NDF-RT N0000175556
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
WHO-VATC QC07AB12
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
WHO-ATC C07FB12
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
WHO-ATC C09DX05
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
NCI_THESAURUS C29576
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
WHO-ATC C07BB12
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
WHO-ATC C07AB12
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
WHO-VATC QC07BB12
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
Code System Code Type Description
DRUG CENTRAL
1887
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
DRUG BANK
DB04861
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
NCI_THESAURUS
C66221
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
MERCK INDEX
M7786
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY Merck Index
EVMPD
SUB09175MIG
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
FDA UNII
030Y90569U
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
ChEMBL
CHEMBL434394
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
LACTMED
Nebivolol
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
IUPHAR
7246
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
CAS
99200-09-6
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
NON-SPECIFIC STEREOCHEMISTRY
RXCUI
31555
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY RxNorm
MESH
C052753
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
WIKIPEDIA
NEBIVOLOL
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
EPA CompTox
99200-09-6
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
INN
5969
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
CAS
118457-14-0
Created by admin on Sat Jun 26 09:33:10 UTC 2021 , Edited by admin on Sat Jun 26 09:33:10 UTC 2021
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET -> AGONIST
SHORT-ACTING
METABOLIC ENZYME -> SUBSTRATE
MINOR
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC IN THE EM POPULATION

FASTED CONDITION

ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC