(±)-Nebivolol-d4 (hydrochloride)

(±)-Nebivolol-d₄ is intended for use as an internal standard for the quantification of nebivolol by GC- or LC-MS. Nebivolol is a potent and selective β₁-adrenergic receptor (β₁-AR) antagonist (IC₅₀s = 7.41 and 251 nM for β₁- and β₂-ARs, respectively, in a radioligand binding assay using rabbit lung membrane preparations).¹ It is also selective for β₁-ARs over serotonin 5-HT_1A and 5-HT₂, α₁- and α₂-adrenergic, histamine H₁, and dopamine D₂ receptors (IC₅₀s = 27.5 and 2,239, 3,162 and >10,000, 5,623, and 10,000 nM, respectively). Nebivolol inhibits cAMP accumulation induced by norepinephrine in primary rat cardiac cells (IC₅₀ = 22 nM) and induces vasodilation in mouse renal arteries via a nitric oxide- and cGMP-dependent mechanism (EC₅₀ = 11.36 μM).^2,3 It decreases contraction of isolated human left ventricular trabeculae induced by isoproterenol but does not exert intrinsic sympathomimetic activity (ISA).⁴ Nebivolol inhibits proliferation of human coronary artery smooth muscle cells (HCASMCs) in the presence and absence of growth factors (IC₅₀s = 6.1, 6.8, 6.4, and 7.7 μM for HCASMCs grown in media containing no growth factor, PDGFBB, basic FGF, and TGF-β1, respectively).⁵ Formulations containing nebivolol have been used to treat hypertension.

1.Pauwels, P.J., Gommeren, W., Van Lommen, G., et al.The receptor binding profile of the new antihypertensive agent nebivolol and its stereoisomers compared with various beta-adrenergic blockersMol. Pharmacol.34(6)843-851(1988) 2.Pauwels, P.J., Leysen, J.E., and Janssen, P.A.β-adrenoceptor-mediated cAMP accumulation in cardiac cells: Effects of nebivololEur. J. Pharmacol.172(6)471-479(1989) 3.Georgescu, A., Pluteanu, F., Flonta, M.L., et al.Nebivolol induces a hyperpolarizing effect on smooth muscle cells in the mouse renal artery by activation of beta-2-adrenoceptorsPharmacology81(2)110-117(2008) 4.Brixius, K., Bundkirchen, A., BÖlck, B., et al.Nebivolol, bucindolol, metoprolol and carvedilol are devoid of intrinsic sympathomimetic activity in human myocardiumBr. J. Pharmacol.133(8)1330-1338(2001) 5.Brehm, B.R., Wolf, S.C., Bertsch, D., et al.Effects of nebivolol on proliferation and apoptosis of human coronary artery smooth muscle and endothelial cellsCardiovasc. Res.49(2)430-439(2001)