An Exploratory Study in Healthy Male Subjects of the Mechanism of Mirabegron‐Induced Cardiovascular Effects

Abstract

To explore the role of β₁ -adrenoceptors (ARs) in the heart rate response to the selective β₃ -adrenoceptor agonist mirabegron, 12 young male volunteers received single oral doses of the nonselective β_1/2 -AR antagonist propranolol (160 mg), the selective β₁ -AR antagonist bisoprolol (10 mg), or placebo on days 1 and 5 of each period in a 3-period crossover study. On day 5, dosing was followed by a supratherapeutic dose of mirabegron (200 mg). Vital signs, impedance cardiography, and plasma renin activity were collected. Mirabegron increased heart rate and systolic blood pressure and reduced stroke volume, whereas cardiac output and diastolic blood pressure were unaffected. Mirabegron-induced changes were attenuated by propranolol and bisoprolol. The data indicate that mirabegron has a positive chronotropic effect at supratherapeutic concentrations, which is at least partly mediated by stimulation of β₁ -AR.