Cardiovascular effects of bevantolol, a selective β₁‐adrenoceptor antagonist with a novel pharmacological profile

Abstract

1Bevantolol was more potent in blocking the chronotropic than the hypotensive effects of isoprenaline in pithed rats. 2 Bevantolol itself induced bradycardia, so that it was not possible to estimate the pA2 from nonparallel dose-response curves relating isoprenaline concentration to tachycardia. 3 Bevantolol caused hypertension in pithed rats, an effect attenuated by phentolamine, implying that bevantolol may be an a-adrenoceptor agonist. 4 Bevantolol potentiated the pressor effects of noradrenaline, the maximum potentiation equalling that produced by prior chemical sympathectomy with guanethidine, implying that bevantolol may block noradrenaline uptake. 5 In isolated atria bevantolol-induced bradycardia was associated with a positive shift in take-off potential, a reduction in the maximum rate of depolarization (Vmax), and a lengthening of action potential duration (APD). No change in the slope of the slow diastolic depolarization occurred except at the highest concentration (18 ymol I -'). 6 In atrial and ventricular muscle bevantolol reduced V and overshoot potential, implying reduction of fast inward sodium current (Class I antiarrhythmic action). 7 In pithed rats bevantolol lengthened the P-R interval in the ECG, and produced atrioventricular (A-V) block, and bundle-branch block. In isolated A-V nodal preparations, intranodal conduction time was greatly increased, implying restriction of inward current through calcium channels responsible for nodal depolarization. 8 Bevantolol had no negative inotropic effect in pithed rats, or in isolated atria, and did not alter the positive inotropic effect of raised extracellular calcium concentration, implying absence of restriction of current through calcium channels controlling contraction of the myocardium.

Pharmacology of antihypertensive agents with multiple actions

“…Bevantolol is a cardioselective ~l-adrenoceptor blocking agent with some additional vasodilator activity, which has not yet been studied in sufficient detail [7]. The ~l-selec-…”

Recent Advances in Pharmaceutical Chemistry–review Iii a New Wave of Beta-Blockers

“…The ublocking activity seen is less potent than that seen with labetalol but does confer some vasodilator action on bevantolol. Bevantolol differs somewhat from the available cardioselective /&blockers in that its cardioselectivity is conferred by the incorporation of a unique group into the side-chain amhe function of the molecule (51). This group also appears to be responsible for its a blocking activity.…”

Peripheral vascular effects of beta‐adrenoceptor blockade: comparison of two agents.

“…The possibility that bevantolol has partial aagonistic activity is interesting (Dukes & Vaughan Williams, 1985), since if centrally acting, this could explain the behaviour of muscle PVR which increased 2 h following the first dose of bevantolol but had fallen at 24 h and was much reduced after the seventh dose. Only receptors with B2-characteristics are represented on the blood vessels supplying muscle, which on stimulation produce vasodilation.…”

“…In a series of acute experiments Dukes & Vaughan Williams (1985) suggested that bevantolol may be an ot-adrenoceptor agonist.…”