DEXNEBIVOLOL

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 Search

SMILES

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

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

Description
Sources: https://www.drugbank.ca/drugs/DB04861 | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_LBL.pdf | http://www.bystolic.com/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/1357130

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Beta-1 adrenergic receptor 158 Target ID: CHEMBL213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2455841 \| https://www.ncbi.nlm.nih.gov/pubmed/2462161 \| https://www.allergan.com/assets/pdf/bystolic_pi \| https://www.ncbi.nlm.nih.gov/pubmed/11309254	Antagonist 2760		0.7 nM [Ki]
Beta-1 adrenergic receptor 158 Target ID: CHEMBL213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21283024 \| https://www.ncbi.nlm.nih.gov/pubmed/1681809	Antagonist 2760		0.35 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 549 Sources: https://www.allergan.com/assets/pdf/bystolic_pi https://www.drugs.com/pro/nebivolol.html https://www.ncbi.nlm.nih.gov/pubmed/19393838	Primary		Approved 8360	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
Hypertension 549 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7596131 https://www.ncbi.nlm.nih.gov/pubmed/7692155 https://www.ncbi.nlm.nih.gov/pubmed/18485134 https://www.ncbi.nlm.nih.gov/pubmed/1357130	Primary		Approved 8360	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

C_max

Value	Dose	Co-administered	Analyte	Population
1.48 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/18083889/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/18083889/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
11 h REVIEW https://pubmed.ncbi.nlm.nih.gov/18083889/	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.8	healthy n = 1 Health Status: healthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.4	unhealthy n = 6545 Health Status: unhealthy Condition: Hypertension Population Size: 6545 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.4	Disc. AE: Headache, Nausea... AEs leading to discontinuation/dose reduction: Headache (0.4%) Nausea (0.2%) Bradycardia (0.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206302s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206302s000lbl.pdf Page: p.1	Disc. AE: Disorder fetal... AEs leading to discontinuation/dose reduction: Disorder fetal Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206302s000lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.8	healthy n = 1 Health Status: healthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.8	healthy n = 1 Health Status: healthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.8	healthy n = 1 Health Status: healthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.8	healthy n = 1 Health Status: healthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.8	healthy n = 1 Health Status: healthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.8	healthy n = 1 Health Status: healthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.8	healthy n = 1 Health Status: healthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.8	healthy n = 1 Health Status: healthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.8	healthy n = 1 Health Status: healthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.8	healthy n = 1 Health Status: healthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.4	unhealthy n = 6545 Health Status: unhealthy Condition: Hypertension Population Size: 6545 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.4	unhealthy n = 6545 Health Status: unhealthy Condition: Hypertension Population Size: 6545 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf Page: p.4	unhealthy n = 6545 Health Status: unhealthy Condition: Hypertension Population Size: 6545 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206302s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206302s000lbl.pdf Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709	inhibitor 1752	substrate 1193 inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2A6 704 CYP2B6 799 CYP2C8 901 CYP2C19 1463 CYP3A4/5 273

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_ClinPharmR_P1.pdf Page: 50, 55	no
CYP2A6 736	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_ClinPharmR_P1.pdf Page: 50, 55	no
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_ClinPharmR_P1.pdf Page: 50, 55	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_ClinPharmR_P1.pdf Page: 50, 55	no
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_ClinPharmR_P1.pdf Page: 50, 55	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_ClinPharmR_P1.pdf Page: 50, 55	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_ClinPharmR_P1.pdf Page: 50, 55	no
CYP3A4/5 330	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_ClinPharmR_P1.pdf Page: 50, 55	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021742s000_ClinPharmR_P1.pdf Page: 28, 50, 55	minor
CYP2D6 1193	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/206302Orig1s000ClinPharmR.pdf 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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/206302Orig1s000ClinPharmR.pdf Page: 17.0

Sourcing

Vendor/Aggregator	ID	URL
AChemBlock	10241
AK Scientific	M753
Aronis	BBC/719
BOC Sciences	118457-15-1
IBScreen	BB_SC-12513
IBScreen	Bio-0068
Lab Network	LN01346236
MolPort	MolPort-003-849-342
MolPort	MolPort-023-276-830
ShangHai Biochempartner	BCP21038
Tocris	3517
Toronto Research Chemicals	N387896
Vitas-M Laboratory	STK637549
ZINC	ZINC000003951631	http://zinc15.docking.org/substances/ZINC000003951631
eMolecules	29703203
eMolecules	300435536
eMolecules	30387256
mcule	MCULE-7932280679

PubMed

Title	Date	PubMed

Beta-blockers of the third generation inhibit endothelin-1 liberation, mRNA production and proliferation of human coronary smooth muscle and endothelial cells.	2000 Nov	11078433
Characterization of beta(1)-selectivity, adrenoceptor-G(s)-protein interaction and inverse agonism of nebivolol in human myocardium.	2001 Apr	11309254
Nebivolol, bucindolol, metoprolol and carvedilol are devoid of intrinsic sympathomimetic activity in human myocardium.	2001 Aug	11498519
Metabolic effects and safety profile of nebivolol.	2001 Dec	11811391
Nebivolol: endothelium-mediated vasodilating effect.	2001 Dec	11811387
Effects of nebivolol on proliferation and apoptosis of human coronary artery smooth muscle and endothelial cells.	2001 Feb 1	11164853
Nebivolol, carvedilol and metoprolol do not influence cardiac Ca(2+) sensitivity.	2001 Jun 22	11430928
[Nebivolol, a beta blocker of the 3rd generation: modern therapy of arterial hypertension. Results of a multicenter observation study].	2001 Mar 15	11293936
Nebivolol and airway responsiveness in the rabbit.	2001 Mar 23	11324721
[Effects of nebivolol, metoprolol and enalapril maleate on the state of endothelium-dependent arteriolar vasodilation in patients with essential hypertension].	2001 Mar-Apr	11519414
[Beta blockers in heart failure administered with too much reticence. Longevity sacrificed].	2001 Nov 29	11770384
[Nebivolol treatment in essential arterial hypertension].	2001 Oct-Dec	12092233
[Effect of nebivolol on the level of constitutional, inducible, and total NO-synthase in serum of patients with type II diabetes mellitus].	2002	12669563
[Effect of enape combined with nebilet in hypertension].	2002	12587324
[Assessment of efficacy and safety of nebivolol in patients with stable effort angina].	2002	12494203
[Experience of the use of nebivolol in the treatment of hypertension in postmenopausal women].	2002	12494089
[Effect of nebivolol on dynamics of microalbuminuria, renal blood flow and 24-hour blood pressure profile in patients with hypertension].	2002	12494075
[Effect of nebivolol on remodeling of the heart and vessels and the state of hemodynamics in patients with hypertension].	2002	12494053
[Assessment of safety and antihypertensive efficacy of a cardioselective beta-blocker nebivolol in patients with hypertension and concomitant chronic obstructive bronchitis].	2002	12494034
[Antihypertensive efficacy and tolerability of nebivolol].	2002	12494015
[Effects of nebivolol on serum levels of NO2 and NO3 oxides in patients with type 2 diabetes mellitus].	2002	11944352
Paradoxical pressor effects of beta-blockers in standing elderly patients with mild hypertension: a beneficial side effect.	2002 Apr 9	11940545
Effect of nebivolol on left ventricular function in patients with chronic heart failure: a pilot study.	2002 Dec	12453547
The pharmacologic treatment of uncomplicated arterial hypertension in patients with airway dysfunction.	2002 Jan	11796456
[Cardiac protection by beta-1 selective beta blocker. Still better in the 3rd generation?].	2002 Jul 11	12198891
Nebivolol ameliorates nitric oxide deficient hypertension.	2002 Jun 20	12806161
[Heart rate control with nebivolol in patients with tachysystolic atrial fibrillation].	2003	14593370
[The use of nebivolol in menopausal women with hypertension].	2003	14593358
[Dynamics of a 24-h profile of arterial pressure and function of the vascular endothelium in nebivolol treatment of hypertensive patients].	2003	14520947
[Pharmacological modulation of NO synthesis in patients with arterial hypertension and endothelial dysfunction].	2003	12934313
[Use of nebivolol in patients with mild and moderate hypertension].	2003	12718224
Nebivolol prevents vascular NOS III uncoupling in experimental hyperlipidemia and inhibits NADPH oxidase activity in inflammatory cells.	2003 Apr 1	12692005
Lack of inverse agonistic activity of nebivolol, its D- and L-enantiomers and of in vivo metabolized nebivolol in human myocardium.	2003 Aug 22	12969754
Efficacy and tolerability profile of nebivolol vs atenolol in mild-to-moderate essential hypertension: results of a double-blind randomized multicentre trial.	2003 Dec	14761075
A comparison of the beta1-selectivity of three beta1-selective beta-blockers.	2003 Jun	12795776
Different effect of antihypertensive drugs on conduit artery endothelial function.	2003 Jun	12719441
Third-generation beta-blockers stimulate nitric oxide release from endothelial cells through ATP efflux: a novel mechanism for antihypertensive action.	2003 Jun 3	12742996
Comparison of the new cardioselective beta-blocker nebivolol with bisoprolol in hypertension: the Nebivolol, Bisoprolol Multicenter Study (NEBIS).	2003 May	14574084
Effects of nebivolol on ischemia-induced metabolic changes in dog hearts.	2003 May	12717108
[Nebivolol in the treatment of ischemic heart disease patients with chronic heart failure].	2004	15029131
[Genetic polymorphisms in drug metabolizing enzymes--impact on treatment with beta-blockers].	2004 Apr 8	15054690
Comparative effects of a two-week treatment with nebivolol and nifedipine in hypertensive patients suffering from COPD.	2004 Mar-Apr	15031571

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 23:28:49 UTC 2023` Edited by `admin` on `Wed Jul 05 23:28:49 UTC 2023`
Record UNII	I43D0296P8
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DEXNEBIVOLOL

Official Name

English

2H-1-BENZOPYRAN-2-METHANOL, .ALPHA.,.ALPHA.'-(IMINOBIS(METHYLENE))BIS(6-FLUORO-3,4-DIHYDRO-, (.ALPHA.R,.ALPHA.'R,2R,2'S)-

Systematic Name

English

Dexnebivolol [WHO-DD]

Common Name

English

R-67138

Code

English

(S,R,R,R)-NEBIVOLOL

Common Name

English

(1R)-2-(((2R)-2-((2S)-6-FLUORO-3,4-DIHYDRO-2H-CHROMEN-2-YL)-2-HYDROXYETHYL)AMINO)-1-((2R)-6-FLUORO-3,4-DIHYDRO-2H-CHROMEN-2-YL)ETHANOL

Systematic Name

English

(+)-NEBIVOLOL

Common Name

English

dexnebivolol [INN]

Common Name

English

D-NEBIVOLOL

Common Name

English

(.ALPHA.R,.ALPHA.'R,2R,2'S)-.ALPHA.,.ALPHA.'-(IMINOBIS(METHYLENE))BIS(6-FLUORO-3,4-DIHYDRO-2H-1-BENZOPYRAN-2-METHANOL)

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29576