U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C22H25F2NO4
Molecular Weight 405.435
Optical Activity ( + / - )
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NEBIVOLOL

SMILES

[H][C@]1(CCC2=CC(F)=CC=C2O1)[C@H](O)CNC[C@@H](O)[C@@]3([H])CCC4=C(O3)C=CC(F)=C4

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 405.435
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. The beta-blocking effects of nebivolol reside in the d-isomer. Nebivolol is a racemic combination of Dexnebivolol (d-nebivolol, +SRRR nebivolol) and l-nebivolol (-RSSS nebivolol) that differs chemically from other beta-blockers, with an absolutely symmetrical configuration developing from a central nitrogen atom. D-nebivolol and l-nebivolol divaricate pharmacologically and therapeutically, with a noticeably different profile from that of conventional beta-blockers; for instance, the selective blocking of beta(1)-adrenoceptors is determined almost exclusively by d-nebivolol. Both enantiomers act synergistically with respect to blood pressure reduction: the effect of nebivolol on heart rate is exclusively exerted by d-nebivolol, with these hypotensive effects enhanced by the addition of the l-enantiomer, which in itself does not influence systolic and diastolic blood pressure. Isomer d-nebivolol (SRRR) is a β1 adrenergic receptor blocker and its antipode, l-nebivolol (RSSS) is responsible for endothelium-dependent NO liberation. 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. The binding affinities of d-nebivolol and nebivolol for human beta 1-adrenergic binding sites correlated well with their potencies in inhibiting beta 1-adrenergic receptor coupled accumulation of cAMP.

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
Beta-blockade with nebivolol enhances the acetylcholine-induced cutaneous vasodilation.
2001 Apr
Nebivolol, bucindolol, metoprolol and carvedilol are devoid of intrinsic sympathomimetic activity in human myocardium.
2001 Aug
Vascular effects of newer cardiovascular drugs: focus on nebivolol and ACE-inhibitors.
2001 Dec
Protective role of nebivolol in hydroxyl radical induced injury.
2001 Dec
Nebivolol: endothelium-mediated vasodilating effect.
2001 Dec
[Heart and lung disease. Are beta blockers allowed in asthma?].
2001 May 24
[Pharma-clinics medication of the month. Nebivolol (Nobiten)].
2001 Nov
Endothelial adrenoceptors.
2001 Nov
[Beta blockers in heart failure administered with too much reticence. Longevity sacrificed].
2001 Nov 29
[Nebivolol (nebilet) a beta blocker of the third generation--also for patients with obstructive lung diseases?].
2001 Oct
What drug must be used to avoid the most common hypertensive complications?
2001 Oct
[Antihypertensive efficacy and tolerability of nebivolol].
2002
Nebivolol vs amlodipine as first-line treatment of essential arterial hypertension in the elderly.
2002
Paradoxical pressor effects of beta-blockers in standing elderly patients with mild hypertension: a beneficial side effect.
2002 Apr 9
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
Hyperkalaemia in an elderly diabetic patient.
2002 Jan
The pharmacologic treatment of uncomplicated arterial hypertension in patients with airway dysfunction.
2002 Jan
[Cardiac protection by beta-1 selective beta blocker. Still better in the 3rd generation?].
2002 Jul 11
Effects of nebivolol and atenolol on small arteries and microcirculatory endothelium-dependent dilation in hypertensive patients undergoing isometric stress.
2002 Sep
Focus on small artery stiffness.
2002 Sep
[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
Lack of inverse agonistic activity of nebivolol, its D- and L-enantiomers and of in vivo metabolized nebivolol in human myocardium.
2003 Aug 22
Efficacy and tolerability profile of nebivolol vs atenolol in mild-to-moderate essential hypertension: results of a double-blind randomized multicentre trial.
2003 Dec
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
[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
Antioxidant activity of nebivolol in the rat aorta.
2004 Jan
Different pharmacological properties of two enantiomers in a unique beta-blocker, nebivolol.
2008 Summer
Patents

Sample Use Guides

Can be taken with and without food. Individualize to the needs of the patient and monitor during up-titration. (2) • Hypertension: Most patients start at 5 mg once daily. Dose can be increased at 2-week intervals up to 40 mg.
Route of Administration: Oral
Nebivolol reduces cell proliferation of human coronary smooth muscle cells (haCSMCs) and endothelial cells (haECs) in a concentration- and time-dependent maner. Nebivolol treatment for 7 days causes significant reduction in cell growth of haCSMCs with IC50 of 6.1 uM, and inhibits accelerated haCSMC proliferation stimulated by growth factors PDGF-BB, bFGF, and TGFβ with IC50 values of 6.8 uM, 6.4 uM and 7.7 uM, repectively. Nebivolol treatment (10-5 M) of haCSMCs for 48 hours induces a moderate apoptosis of 23% and a decrease from 16% to 5% in the number of cells in S-phase. During Nebivolol incubation, NO formation of HaCEs increases, while endothelin-1 transcription and secretion are suppressed.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:09:50 UTC 2023
Edited
by admin
on Wed Jul 05 23:09:50 UTC 2023
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
Nebivolol [WHO-DD]
Common Name English
NARBIVOLOL
Common Name English
BYVALSON COMPONENT 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
Classification Tree Code System Code
LIVERTOX NBK548386
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
NDF-RT N0000175556
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
WHO-VATC QC07AB12
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
WHO-ATC C07FB12
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
WHO-ATC C09DX05
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
NCI_THESAURUS C29576
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
WHO-ATC C07BB12
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
WHO-ATC C07AB12
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
WHO-VATC QC07BB12
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
Code System Code Type Description
SMS_ID
100000093044
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
DRUG CENTRAL
1887
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
DRUG BANK
DB04861
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
NCI_THESAURUS
C66221
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
MERCK INDEX
M7786
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY Merck Index
USAN
Y-62
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
EVMPD
SUB09175MIG
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
DAILYMED
030Y90569U
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
FDA UNII
030Y90569U
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
ChEMBL
CHEMBL434394
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
LACTMED
Nebivolol
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
IUPHAR
7246
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
CAS
99200-09-6
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
NON-SPECIFIC STEREOCHEMISTRY
CHEBI
64022
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
RXCUI
31555
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY RxNorm
EPA CompTox
DTXSID9040556
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
MESH
C052753
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
WIKIPEDIA
NEBIVOLOL
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
INN
5969
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
CAS
118457-14-0
Created by admin on Wed Jul 05 23:09:50 UTC 2023 , Edited by admin on Wed Jul 05 23:09:50 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> AGONIST
SHORT-ACTING
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
MAJOR
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