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
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
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 |
DescriptionSources: https://www.drugbank.ca/drugs/DB04861 | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_LBL.pdf | https://www.ncbi.nlm.nih.gov/pubmed/18485134 | https://www.ncbi.nlm.nih.gov/pubmed/9825177 | https://www.ncbi.nlm.nih.gov/pubmed/21283024 | https://www.ncbi.nlm.nih.gov/pubmed/1681809 | https://www.ncbi.nlm.nih.gov/pubmed/1357130https://www.drugbank.ca/drugs/DB04861 | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_LBL.pdf | http://www.bystolic.com/
Sources: https://www.drugbank.ca/drugs/DB04861 | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_LBL.pdf | https://www.ncbi.nlm.nih.gov/pubmed/18485134 | https://www.ncbi.nlm.nih.gov/pubmed/9825177 | https://www.ncbi.nlm.nih.gov/pubmed/21283024 | https://www.ncbi.nlm.nih.gov/pubmed/1681809 | https://www.ncbi.nlm.nih.gov/pubmed/1357130https://www.drugbank.ca/drugs/DB04861 | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_LBL.pdf | http://www.bystolic.com/
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.
CNS Activity
Sources: https://link.springer.com/article/10.1007/BF03258299 | https://books.google.ru/books?id=2Q5hCgAAQBAJ&pg=PA188&lpg=PA188&dq=nebivolol retrieved from Pharmacotherapeutics For Advanced Practice Nurse Prescribers By Teri Moser Woo, Marylou V Robinson, p.188https://link.springer.com/article/10.1007/BF03258299 | https://books.google.ru/books?id=2Q5hCgAAQBAJ&pg=PA188&lpg=PA188&dq=nebivolol retrieved from Pharmacotherapeutics For Advanced Practice Nurse Prescribers By Teri Moser Woo, Marylou V Robinson, p.188 | https://www.ncbi.nlm.nih.gov/pubmed/23128558
Curator's Comment: Nebivolol is a highly lipophilic drug and, thus, it may penetrate the central nervous system (CNS) in humans.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
0.7 nM [Ki] | |||
Target ID: CHEMBL213 |
0.35 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | BYSTOLIC Approved UseBYSTOLIC 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 Date2007 |
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Primary | BYSTOLIC Approved UseBYSTOLIC 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 Date2007 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2% |
unknown |
NEBIVOLOL plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse 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 Sources: Page: p.8Pallor Depressed level of consciousness Hypokinesia Hypotension Sinus bradycardia Hypoglycemia Hypokalemia Respiratory failure Vomiting |
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%) Sources: Page: p.4Nausea (0.2%) Bradycardia (0.2%) |
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
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 50, 55 |
no | |||
Page: 50, 55 |
no | |||
Page: 50, 55 |
no | |||
Page: 50, 55 |
no | |||
Page: 50, 55 |
no | |||
Page: 50, 55 |
no | |||
Page: 50, 55 |
no | |||
Page: 50, 55 |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 28, 50, 55 |
minor | |||
Page: 17.0 |
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
Title | Date | PubMed |
---|---|---|
Relationship between the sympatholytic action of nebivolol and hypotension. | 1992 Jul |
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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 |
|
Studies on the effect of alcohols on the chiral discrimination mechanisms of amylose stationary phase on the enantioseparation of nebivolol by HPLC. | 2001 Apr 24 |
|
Protective role of nebivolol in hydroxyl radical induced injury. | 2001 Dec |
|
Effects of nebivolol on proliferation and apoptosis of human coronary artery smooth muscle and endothelial cells. | 2001 Feb 1 |
|
[Pharma-clinics medication of the month. Nebivolol (Nobiten)]. | 2001 Nov |
|
Endothelial adrenoceptors. | 2001 Nov |
|
[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 |
|
[Effects of nebivolol on microcirculation, platelet aggregation and blood viscosity in patients with essential hypertension]. | 2002 |
|
Effects of antihypertensive drugs on endothelial dysfunction: clinical implications. | 2002 |
|
Paradoxical pressor effects of beta-blockers in standing elderly patients with mild hypertension: a beneficial side effect. | 2002 Apr 9 |
|
Effect of nebivolol on left ventricular function in patients with chronic heart failure: a pilot study. | 2002 Dec |
|
The pharmacologic treatment of uncomplicated arterial hypertension in patients with airway dysfunction. | 2002 Jan |
|
Nebivolol ameliorates nitric oxide deficient hypertension. | 2002 Jun 20 |
|
[Despite antihypertensive treatment with beta-blocker patients remain incapacitated]. | 2002 May 2 |
|
Nebivolol: a selective beta(1)-adrenergic receptor antagonist that relaxes vascular smooth muscle by nitric oxide- and cyclic GMP-dependent mechanisms. | 2002 Sep |
|
Allergic contact dermatitis to nebivolol. | 2002 Sep |
|
[Nebivolol effects on platelet aggregation and anticoagulation system]. | 2003 |
|
[The use of nebivolol in menopausal women with hypertension]. | 2003 |
|
[Pharmacological modulation of NO synthesis in patients with arterial hypertension and endothelial dysfunction]. | 2003 |
|
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 |
|
Lack of inverse agonistic activity of nebivolol, its D- and L-enantiomers and of in vivo metabolized nebivolol in human myocardium. | 2003 Aug 22 |
|
Beta 1-adrenoceptor selectivity of nebivolol and bisoprolol. A comparison of [3H]CGP 12.177 and [125I]iodocyanopindolol binding studies. | 2003 Jan 26 |
|
Effects of nebivolol on ischemia-induced metabolic changes in dog hearts. | 2003 May |
|
[Beta-1 blockade plus NO release. Additional organ protection for patients with hypertension]. | 2003 Oct 2 |
|
Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats. | 2003 Sep |
|
[Genetic polymorphisms in drug metabolizing enzymes--impact on treatment with beta-blockers]. | 2004 Apr 8 |
|
Different pharmacological properties of two enantiomers in a unique beta-blocker, nebivolol. | 2008 Summer |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7596131
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2575531
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
Edited
Fri Dec 15 15:40:54 GMT 2023
by
admin
on
Fri Dec 15 15:40:54 GMT 2023
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Record UNII |
030Y90569U
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Record Status |
Validated (UNII)
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Record Version |
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LIVERTOX |
NBK548386
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NDF-RT |
N0000175556
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WHO-VATC |
QC07AB12
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WHO-ATC |
C07FB12
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WHO-ATC |
C09DX05
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NCI_THESAURUS |
C29576
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C07BB12
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C07AB12
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WHO-VATC |
QC07BB12
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100000093044
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1887
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DB04861
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C66221
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m7786
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CHEMBL434394
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Nebivolol
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C052753
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NEBIVOLOL
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118457-14-0
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BINDER->LIGAND |
BINDING
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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METABOLIC ENZYME -> SUBSTRATE |
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SALT/SOLVATE -> PARENT |
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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