Local anaesthetic and anti‐arrhythmic actions of alprenolol relative to its effect on intracellular potentials and other properties of isolated cardiac muscle

Abstract

1 Alprenolol, a β-adrenoceptor blocking drug reported to have the same potency as propranolol in vitro and in vivo, was found to be four times more active than procaine as a local anaesthetic on frog sciatic nerve. 2 At doses of 0·125 mg/kg and above alprenolol protected anaesthetized guinea-pigs against ouabain-induced ventricular fibrillation. 3 In isolated rabbit atria, resting potentials were unchanged, and the duration of the action potential was not prolonged, by concentrations of alprenolol up to 10·5 × 10⁻⁶m. The maximum rate of depolarization (MRD), however, was reduced by 30% at a concentration of 0·525 × 10⁻⁶m. This was 214 times less than the concentration which reduced the frog action potential height by 25%. 4 The concentration of alprenolol required to produce more than 15% decrease in contraction or maximum driven frequency was 3·5 × 10⁻⁶m. 5 As a test of the direct action of alprenolol on isolated cardiac muscle, MRD was also a more sensitive test than the measurement of electrical threshold or conduction velocity.