Nebivolol: Pharmacologic Profile of an Ultraselective, Vasodilatory β¹‐Blocker

Abstract

Beta-blockers are well-established therapeutic agents in the treatment of hypertension and cardiovascular disease. However, these agents are highly heterogeneous. Beta-blockers differ in their ancillary pharmacologic properties, which are clinically important. Nebivolol is a highly selective beta(1)-adrenergic receptor blocker that induces vasodilation through stimulation of the endothelial nitric oxide/L-arginine pathway. As a racemic mixture of d- and l-enantiomers, nebivolol is highly lipophilic and rapidly absorbed. Nebivolol undergoes extensive hepatic metabolism through the cytochrome P450 2D6 (CYP2D6) system. As a result of genetic polymorphisms, CYP2D6 has variable activity, manifested by extensive and poor metabolizers of nebivolol. Time to maximum concentration is 0.5 to 2 hours, and half-life is 11 hours in extensive metabolizers; these values are about 3 times longer in poor metabolizers. Urinary and fecal excretion of unchanged nebivolol is less than 0.5% of the dose. Nebivolol has a unique hemodynamic profile of reduced systemic vascular resistance and increased left ventricular function. These properties are attributed to its vasodilating action and contrast with the hemodynamic effects of conventional beta-blockers. Nebivolol is thus a novel beta-blocker with several important pharmacologic properties that distinguish it from traditional beta-blockers. These unique properties may confer clinical benefits beyond simple blood pressure lowering.

Lipid Simulations: A Perspective on Lipids in Action

“…b2-AR activity induces smooth muscle relaxation; thus, b2-AR blockade is commonly used in asthma inhalers (Taylor 2007). Meanwhile, nebivolol is a new, highly selective b1-AR blocker (Prisant et al 2008) characterized by lack of side effects that are otherwise typical for b-blockers, and also lack of interactions with other drugs (Veverka et al 2006). Nebivolol has four chiral centers and 10 stereoisomers, though only two of them are of pharmaceutical interest: the srrr-form and the rsss-form (Siebert et al 2008).…”

Nebivolol Treatment Reduces Serum Levels of Asymmetric Dimethylarginine and Improves Endothelial Dysfunction in Essential Hypertensive Patients

“…17 Recently, in an in vitro study we demonstrated that nebivolol increased the expression and activity of DDAH2 in endothelial cells. 18 Although nebivolol has been shown to reverse endothelial dysfunction 4 and several studies have investigated nebivolol-induced vasodilating effect, the precise molecular mechanism(s) is still under investigation. In this study, we first compared the effect of nebivolol with atenolol, a traditional selective β1-adrenergic receptor blocker without vasodilating properties, on plasma ADMA concentrations and on brachial artery (BA) flow-mediated dilation (FMD) in patients with essential hypertension.…”

The effect of nebivolol on P wave duration and dispersion in patients with Behçet’s disease; a prospective single-arm controlled study

“…So, it is reasonable to suggest that the decrease in maximum P wave duration and PD measured at the end of the nebivolol therapy may be related with the attenuation of the actions of the sympathetic nervous system on atrial electrical physiology. Nebivolol promote nitric oxide bioactivity and vasodilatation by inhibiting oxidative stress and inflammation (45). Furthermore, nebivolol reduced coronary artery smooth muscle cell growth (46,47).…”