A qualitative distinction between the beta-receptor-blocking and local anesthetic actions of antiarrhythmic agents.

Fragmented cardiac sarcoplasmic reticulum was isolated by differential centrifugation from canine myocardium. The effects of propranolol, quinidine, lidocaine (lignocaine) and tetracaine (amethocaine) on calcium uptake in sarcoplasmic reticulum in vitro were then measured. All the drugs are antiarrhythmic agents with local anesthetic activity, but propranolol and quinidine are known also to have beta-receptor-blocking actions in that they can prevent the cardiac effects of isoprenaline and depress the myocardium. Lidocaine and tetracaine do not generally depress the heart and had no effect on the calcium uptake, but propranolol and quinidine both significantly inhibited it. It was concluded that the antiarrhythmic actions of propranolol (and quinidine) may be independent of beta-receptor-blocking activity, and that the safety of lidocaine as an antiarrhythmic agent may be related to a lack of effect on the sarcoplasmic reticulum. ADDITIONAL