Bevantolol

Bevantolol (SOM3355 (free base)) is a selective β1-adrenergic receptor antagonist, with an IC₅₀ of 35 nM for β₁-adrenergic receptor and an IC₅₀ of 60 nM for VMAT2. Bevantolol blocks β1-adrenergic receptors, exerts partial agonistic effects on α-adrenoceptor, inhibits calcium currents in the sinoatrial and atrioventricular nodes as well as sodium currents in cardiomyocytes, delays repolarization, and shortens the action potential duration of Purkinje cells. Bevantolol reduces peripheral vascular resistance, increases subendocardial blood flow, inhibits VMAT2, elevates the serum HDL/LDL ratio, and does not affect glomerular filtration rate or cause cold extremities. Bevantolol is applicable to research related to angina pectoris, hypertension, arrhythmia, and Huntington's disease^[1][2][3]. In Vitro:Bevantolol (1.0-10.0 μmol/L) directly reduces the spontaneous rate of isolated rabbit atria^[1].
Bevantolol potently inhibits the β₁-adrenergic receptor with an IC₅₀ of 35 nM^[2].
Bevantolol blocks the isoproterenol-induced chronotropic response in isolated rabbit atria, with a pA₂ value of approximately 7.6 to 8.1^[1].
Bevantolol exhibits 32-fold higher affinity for β-1 adrenergic receptors in guinea pig atria (K_B = 0.9 × 10^-8) than for β-2 adrenergic receptors in guinea pig trachea (K_B = 3.0 × 10^-7)^[1].
Bevantolol (2-8 μmol/L) inhibits the inward calcium current in rabbit sinoatrial and atrioventricular nodal cells, reduces MRD and shifted pacemaker potential, and delays repolarization, thereby inducing bradycardia without affecting the slope of diastolic slow potential^[1].
Bevantolol (2-8 μmol/L) exerts class I antiarrhythmic effects on rabbit atrial cells, Purkinje cells and ventricular cells, reduces the MRD of most cells, delays repolarization, and shortens the action potential duration of preterminal Purkinje cells^[1].
Bevantolol exerts no negative inotropic effect on rabbit atrial or ventricular cardiomyocytes, nor does it inhibit calcium-mediated positive inotropic effects^[1].
Bevantolol exhibits higher binding affinity for α-1 adrenergic receptors in rat brain cell membranes than norepinephrine^[1].
Bevantolol acts as an α-adrenergic receptor antagonist in isolated rabbit aortic strips, inhibits phenylephrine-induced contractions, and has no agonist activity^[1].
Bevantolol (1-10 μM) induces dose-dependent bradycardia, inhibits calcium-induced tachycardia, and blocks β-adrenergic receptors without exerting negative inotropic effects in isolated rabbit atria^[3].
Bevantolol (2-8 μM; 40 min) dose-dependently decreases the heart rate, peak action potential amplitude, and depolarization/repolarization rate of rabbit sinoatrial node cells and sinoatrial node transitional cells, while increasing the pacemaker potential and prolonging the repolarization duration^[3].
Bevantolol (2-8 μM; 40 min) dose-dependently prolongs the conduction time of the atrioventricular conduction pathway in rabbits, with the strongest inhibitory effect on the atrioventricular node itself. It also reduces the depolarization rate of atrioventricular node cells and prolongs the action potential duration^[3].
Bevantolol (2-8 μM; 40 min) reduces the maximum depolarization rate and action potential amplitude in a dose-dependent manner, alters action potential duration in a region-specific manner, and has no effect on the resting potential of rabbit prepurkinje and purkinje cells^[3].
Bevantolol (2-8 μM; 40 min) reduces the maximum depolarization rate and action potential amplitude of rabbit atrial and ventricular cardiomyocytes in a dose-dependent manner, and prolongs the action potential duration^[3].
Bevantolol exhibits inhibitory effects on VMAT2, with an IC₅₀ value of 60 nM^[2]. In Vivo:Bevantolol (0.72-18.0 μmol/kg; intravenous injection; single administration) is selective for β-1 adrenergic receptors, induces dose-dependent bradycardia in spinal cord-transected rats, and exhibits no intrinsic sympathomimetic activity in catecholamine-depleted rats^[1].
Bevantolol (0.3-10.0 mg/kg; intravenous injection; single administration) induces dose-dependent increases in mean blood pressure, decreases in heart rate, and potentiates the pressor response induced by phenylephrine in pentobarbital-anesthetized spinal rats^[1].
Bevantolol (1.0 mg/kg; intravenous injection; single administration) significantly improves subendocardial blood flow and systolic function in the ischemic region of dogs with partial coronary artery occlusion^[1].
Bevantolol (0.3-10 mg/kg; intravenous injection; single administration) induces variable hemodynamic effects in anesthetized dogs, accompanied by dose-dependent changes in total peripheral resistance and mean arterial pressure, and also increases cardiac output and total peripheral resistance in dogs after coronary artery ligation^[1].
Bevantolol (1.0-1.5 mg/kg; intravenous injection; single administration) induces dose-dependent decreases in mean arterial pressure, bradycardia, and reduced cardiac output in anesthetized, thoracotomized Sus scrofa domesticus with high baseline sympathetic nerve activity^[1].
Bevantolol (0.72-18.0 μmol/kg; intravenous injection; cumulative administration every 30 min) acts as a β₁-selective adrenoceptor antagonist in spinal cord-transected rats, producing dose-dependent bradycardia, hypertension, enhanced norepinephrine-induced pressor responses, and atrioventricular/bundle branch block, with minimal effects on isoproterenol-mediated β₂-dependent hypotensive responses at lower doses^[3].
Bevantolol (intravenous injection, 0.2-10.0 mg/kg) induces bradycardia and mild hypotension in anesthetized dogs, and selectively blocks β₁ receptor-mediated effects of isoproterenol; high doses increase blood pressure and peripheral vascular resistance, while moderate doses improve stroke volume after coronary artery ligation^[3].