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Effects on cardiac muscle of the β‐adrenoceptor blocking drugs INPEA and LB46 in relation to their local anaesthetic action on nerve

1 As a local anaesthetic on frog nerve, LB46 had 0·4 times the activity of procaine and 2 times that of INPEA. 2 In reducing the maximum rate of depolarization (MRD) of intracellularly recorded cardiac action potentials, LB46 was 20 times more potent than INPEA. 3 As an antagonist of the chronotropic effect on atrial muscle and of the inotropic effects on ventricular muscle of isoprenaline the pA2 values for LB46 were 9·05 ± 0·15 and 9·30 ± 0·06 respectively, and for INPEA 6·00 ± 0·16 and 6·10 ± 0·12. 4 LB46 was 8 times more active than racemic propranolol in blocking the effects of isoprenaline on isolated cardiac muscle, and since its direct action on the cardiac membrane was only 0·1 times that of propranolol, there was a net gain of 80 times in the specificity of LB46 for class 2 (antisympathetic) over class 1 (depression of MRD) antidysrhythmic actions. 5 INPEA was 2·5 times less active as a β‐adrenoceptor blocking drug on cardiac muscle than (+)‐propranolol, and 1,300 times less active than LB46. 6 INPEA, but not LB46, prolonged the duration of both atrial and ventricular intracellular action potentials.