Nebivolol

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Biological Activity

Description	Nebivolol selectively inhibits β1-adrenoceptor with IC50 of 0.8 nM.
Targets	β1-adrenoceptor
IC50	0.8 nM [1]
In vitro	Nebivolol shows high affinity and selectivity for beta 1-adrenergic receptor sites in a rabbit lung membrane preparation (Ki value = 0.9 nM and beta 2/beta 1 ratio = 50). [1] Nebivolol displays β1-adrenoceptor selectivity with the Ki(β2)/Ki(β1) value of 40.7 judged by competition experiments to 3H-CGP 12.1777 in the presence of CGP 207.12 A (300 nM, Kiβ2) or ICI 118.551 (50 nM, Kiβ1). [2] 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 μM, and inhibits accelerated haCSMC proliferation stimulated by growth factors PDGF-BB, bFGF, and TGFβ with IC50 values of 6.8 μM, 6.4 μM and 7.7 μM, 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. [3]
In vivo	Administratiion of Nebivolol (initially by iv within 10 minutes of reperfusion and then orally) to rats with myocardial infarction (MI) reduces myocardial apoptosis, which is mediated by regulation of NO . Nebivolol, significantly, prevents left ventricular (LV) pressure changes, reduces total and regional apoptotic cardiomyocytes. Nebivolol treatment lowers mean blood pressure (MBP) in rats with MI slightly, but not significantly. [4]
Features	A highly cardioselective compound under certain conditions.

Protocol(Only for Reference)

Cell Assay: [3]

Cell lines	Human coronary smooth muscle cells (haCSMCs) and endothelial cells (haECs)
Concentrations	Dissolved in 100% methanol and diluted with three volumes of growth medium to obtain a stock solution of 10-3 M, final concentration 10-7~10-5 M
Incubation Time	1, 2, 4, 7 and 14 days
Method	Cells are exposed to different concentrations of Nebivolol (10-7~10-5 M) for 1, 2, 4, 7 and 14 days. Cell proliferation is analyzed by bromodeoxyuridine (BrdU) incorporation, and cell apoptosis is detected by PI or annexin V staining.

Animal Study: [4]

Animal Models	Male Sprague Dawley rat myocardial infarction (MI) model
Dosages	2.0 mg/kg
Administration	Gastric gavage once daily

1

References

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT02053246	Recruiting	Pulmonary Hypertension|Diastolic Heart Failure|Heart Failure With Preserved Ejection Fraction	University of Illinois at Chicago|Julio Duarte		Phase 4
NCT01665508	Recruiting	Microvascular Angina	Massachusetts General Hospital|Forest Laboratories		Phase 4
NCT01885988	Recruiting	Erectile Dysfunction	The Miriam Hospital|Martin M. Miner, MD|Forest Laboratories		Phase 4
NCT01771406	Not yet recruiting	Hypertension|Endothelial Dysfunction|Obstructive Sleep Apnea	Universitaire Ziekenhuizen Leuven		Phase 4
NCT01996085	Recruiting	Arterial Hypertension	Military Institute of Medicine, Poland

Chemical Information

Download Nebivolol SDF

Chemical Name	2H-1-Benzopyran-2-methanol, α,α’[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-, hydrochloride, [2R*[R*[R*(S*)]]]-(±)-

Preparing Stock Solutions

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.4419	4.419	8.838	13.257