Nebivolol hydrochloride (R-65824)

2 years -80 in solvent

Gastric gavage once daily

Human coronary smooth muscle cells (haCSMCs) and endothelial cells (haECs)

Dissolved in 100% methanol and diluted with three volumes of growth medium to obtain a stock solution of 10-3 M, final concentration 10-7ca.10-5 M

Dissolved in DMSO and diluted in saline

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, beta1-adrenoceptor selectivity with the Ki(beta2)/Ki(beta1) value of 40.7 judged by competition experiments to 3H-CGP 12.1777 in the presence of CGP 207.12 A (300 nM, Kibeta2) or ICI 118.551 (50 nM, Kibeta1). [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 uM, and inhibits accelerated haCSMC proliferation stimulated by growth factors PDGF-BB, bFGF, and TGFbeta 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. [3]

1, 2, 4, 7 and 14 days

DMSO 88 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL

2H-1-Benzopyran-2-methanol, , '-[iminobis(methylene)]bis[6-fluoro-3, 4-dihydro-, hydrochloride, [2R*[R*[R*(S*)]]]-()-