The pharmacology of 5-(2-t-butylamino-1-hydroxyethyl) salicylamide (AH 3474), a β-adrenoreceptor blocking agent

Abstract

Abstract AH 3474 is a specific β-adrenoreceptor antagonist, devoid of stimulant activity. When given by mouth to conscious guinea-pigs and dogs, AH3474 and propranolol are equiactive in antagonizing isoprenaline-induced tachycardia. In anaesthetized animals AH 3474 was 2–4 times less active than propranolol when given intravenously. A similar potency ratio was found in volunteer studies in which the drug was taken orally. On isolated tissues AH 3474 was much less active than propranolol. AH 3474 had 1/10th the activity of propranolol in blocking the inhibitory action of isoprenaline on the rat uterus and was at least 100 times less active in antagonizing the tachycardia induced by adrenaline on the guinea-pig atria. In vitro, equilibrium conditions for AH 3474 were obtained in 15 min, whereas 45 min were required for propranolol. AH 3474 antagonized the cardiac arrhythmias induced by ouabain in the anaesthetized dog. The amount required far exceeded the β-adrenoreceptor blocking dose. AH 3474 possessed no “quinidine-like” actions on cardiac muscle of dog or guinea-pig. The local anaesthetic activity of AH 3474 was 400 times less than that of propranolol.