Anti‐arrhythmic, local anaesthetic, and adrenergic blocking activity of some β‐receptor antagonists

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Abstract
The antagonistic effect of the β‐receptor blocking compounds propranolol, Ph QA 33 and INPEA on ouabain‐induced cardiac fibrillations in guinea‐pigs was compared with their local anaesthetic and β‐receptor blocking properties. All three compounds were found capable of increasing the tolerance to ouabain and of reversing ouabain‐induced fibrillations, the ED50 being 0.3 mg/kg intravenously, 0.5 mg/kg intravenously, and 1.5 mg/kg intravenously, respectively for propranolol, Ph QA 33 and INPEA. Propranolol and Ph QA 33 were found to be moderate to strong local anaesthetics while INPEA had a considerably weaker though significant effect. The order of potency as β‐receptor blocking compounds was propranolol ≥ Ph QA 33 > INPEA, the latter compound being less than 1% as active as propranolol. Despite the surprising finding that INPEA was effective against non‐catecholamine‐induced arrhythmias, the results support the general assumption that the anti‐arrhythmic effect of β‐receptor blocking compounds is related to their local anaesthetic action rather than to their β‐blocking ability.

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