Nebivolol: Does the key lie in β3 agonism?

Abstract

Beta-blockers are drugs indicated in the treatment of multiple cardiovascular pathologies. The review highlights the mechanisms of action of Nebivolol and its particular potential effect on β3 receptors that increases nitric oxide that may mark very significant differences, which are traduced to benefits in clinical results.Nebivolol has an special place in the treatment of adrenergic hypertension associated with tachycardia and emotional stress, more frequently in young individuals, and may be considered adequate even in patients with glucose and lipid metabolism disorders due to its pleiotropic effect.In patients with heart failure, Nebivolol showed effectiveness and safety in patients over 75 years old.Nebivolol showed a reduction of cardiomyocyte apoptosis and improvement of contractile function through a mechanism related to β3 receptor agonism after an acute coronary syndrome.Because of all these actions Nebivolol should be considered not only a third-generation Beta-blocker.

Multitargeting in cardioprotection: An example of biaromatic compounds

“…[228] Though nebivolol has a much lower affinity for β3than for β1or β2-ARs (pK i [β3] = 5.6 vs. pK i [β1] = 9.17 and pK i [β2] = 7.96) [229] the direct binding of nebivolol to the β3-receptor remains one of the most attractive concepts that explains its specific endothelial vasodilation. [230][231][232][233] The effects of nebivolol on the vascular system, which are attributed to the eNOS enzyme, were observed in humans. It was found that nebivolol had direct endothelium-dependent vasodilation effects and increased the reactivity to stimuli such as hyperemia in both the arterial and venous circulation.…”

“…Though nebivolol has a much lower affinity for β3‐ than for β1‐ or β2‐ARs ( pK i [β3] = 5.6 vs. pK i [β1] = 9.17 and pK i [β2] = 7.96) [ 229 ] the direct binding of nebivolol to the β3‐receptor remains one of the most attractive concepts that explains its specific endothelial vasodilation. [ 230–233 ]…”