Nebivolol HCl

• Catalog No.: S1549
• CAS Number: 152520-56-4
• M. F.: C22H26ClF2NO4
• M. W.: 441.8959464
• Storage: -20°C

SYNONYMS

• IUPAC name: (1R)-1-[(2R)-6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl]-2-{[(2R)-2-[(2S)-6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl]-2-hydroxyethyl]amino}ethan-1-ol hydrochloride
• IUPAC Traditional name: dexnebivolol hydrochloride
• Synonyms: Bystolic; R-67145

DATABASE IDS

• CAS Number: 152520-56-4

PROPERTIES

• Target: adrenergic receptor
• Salt Data: HCL
• Storage Condition: -20°C

DETAILS

Description (English)

Research Area

• Description: Cardiovascular Disease

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 (K_i value = 0.9 nM and beta 2/beta 1 ratio = 50). ^[1] Nebivolol displays β1-adrenoceptor selectivity with the K_i(β2)/K_i(β1) value of 40.7 judged by competition experiments to ^3H-CGP 12.1777 in the presence of CGP 207.12 A (300 nM, K_iβ2) or ICI 118.551 (50 nM, K_iβ1). ^[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]
• Clinical Trials: A Phase IV study of comparative effects of Nebivolol versus Metoprololon on fatigue and quality of life has been completed.
• Features: Nebivolol is highly cardioselective under certain circumstances.

Protocol

• Protocol: 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
• Methods: 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.
• Protocol: Animal Study ^[4]
• Animal Models: Male Sprague Dawley rat myocardial infarction (MI) model
• Formulation: Dissolved in DMSO and diluted in saline
• Doses: 2.0 mg/kg
• Administration: Gastric gavage once daily

References

• References: [1] Pauwels PJ, et al. Mol Pharmacol, 1988, 34(6), 843-851.
• References: [2] Brixius K, et al. Br J Pharmacol, 2001, 133(8), 1330-1338.
• References: [3] Brehm BR, et al. Cardiovasc Res, 2001, 49(2), 430-439.
• References: [4] Mercanoglu G, et al. Circ J, 2008, 72(4), 660-670.

REFERENCES

• Pauwels PJ, et al. Mol Pharmacol, 1988, 34(6), 843-851.
• Brixius K, et al. Br J Pharmacol, 2001, 133(8), 1330-1338.
• Brehm BR, et al. Cardiovasc Res, 2001, 49(2), 430-439.
• Mercanoglu G, et al. Circ J, 2008, 72(4), 660-670.