Pharmacological Mechanisms of Clinically Favorable Properties of a Selective β1‐Adrenoceptor Antagonist, Nebivolol

Abstract

Nebivolol is a racemic mixture of d- and l-enantiomers. The drug is characterized by beta(1)-adrenoceptor selectivity and long-acting beta-blockade exerted predominantly by d-enantiomer. Nebivolol is devoid of intrinsic sympathomimetic activity and has no relevant membrane stabilizing action. Antiproliferative properties of nebivolol were demonstrated in endothelial and smooth muscle cell cultures. Infusion of nebivolol causes a vasodilation in all vascular beds by endothelial-dependent mechanism involving stimulation of beta(3)-adrenoceptors as well as by endothelial-independent mechanism. Nebivolol possesses not only direct vasodilator properties but also augments the action of endothelium-dependent vasodilators. The antioxidant property of nebivolol can at least in part explain why treatment with this drug enhances eNOS activity and minimizes the reperfusion-induced myocardial injury. The systemic effects of nebivolol in humans have an unusual hemodynamic profile. In contrast to traditional beta-adrenoceptor antagonists, nebivolol reduces preload and afterload due to systemic vasodilation and improves arterial distensibility. At 5 mg daily nebivolol effectively reduces systolic and diastolic blood pressure over a 24-h period. During treatment with nebivolol arterial pressure follows the natural circadian rhythm. Trough-to-peak ratio for nebivolol is 0.9. It has been demonstrated in numerous placebo-controlled studies that exercise tolerance is not reduced during nebivolol therapy. By chronic administration to patients with left ventricular dysfunction nebivolol increases myocardial contractility. Nebivolol produced no significant changes in lipid levels, insulin sensitivity or glucose tolerance. These findings make nebivolol a promising therapeutic tool for the treatment of arterial hypertension and chronic heart failure.

Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome

“…In contrast, third-generation agents, such as nebivolol and carvedilol, possess vasodilator actions through such proposed mechanisms as NO release, antioxidant effects, β 2 agonism, and calcium blockade [108,109]. These vasodilating agents have beneficial or neutral effects on insulin sensitivity and glycemic control [82,[109][110][111].…”

“…Third-generation β-blockers also have neutral or favorable effects on lipid parameters [106,109,111]. Representative older and third-generation β-blockers have demonstrated antioxidant properties, including the ability to scavenge ROS, but thirdgeneration agents have shown these effects more consistently [111,[113][114][115][116].…”

“…These vasodilating agents have beneficial or neutral effects on insulin sensitivity and glycemic control [82,[109][110][111]. Nebivolol, a highly selective β1 receptor blocker, has been shown to increase vascular NO production and reduce NADPH oxidase-mediated generation of ROS [112,113].…”

Comparative Pharmacokinetics and Effect on the Hemodynamics of Original and Generic Nebivolol in Healthy Volunteers

“…Полученные результаты хорошо согласуются с дан-ными литературы [15][16][17]. Для всех параметров значимых различий сравниваемых величин не от-мечалось.…”

Nebivolol, But Not Metoprolol, Treatment Improves Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure

“…Nebivolol, a third‐generation β‐blocker with high selectivity for β 1 ‐adrenergic receptors and unique antioxidant effects, has proven to be highly effective in treating hypertension 9, 10, 11. Nebivolol exhibits unique properties that distinguish it from other β‐blockers.…”