A comparison of the anti-arrhythmic actions of I.C.I. 50172 and (--)-propranolol and their effects on intracellular cardiac action potentials and other features of cardiac function.
1. I.C.I. 50172 had marked quinidine-like effects on intracellular cardiac action potentials at concentrations above 20 mg/l. (6.61 x 10(-5)M). The rate of rise and overshoot of the action potential, conduction velocity and contractions were decreased. (-)-Propranolol had similar effects at less than 1/30 this concentration.2. I.C.I. 50172 had 1/100 the activity of (-)-propranolol as a local anaesthetic. Since this is also the ratio of their in vitro beta-receptor blocking activities, I.C.I. 50172 provides no net increase in specificity of beta-receptor blockade.3. In contrast, the in vivo activity of I.C.I. 50172 in protecting anaesthetized guinea-pigs against ouabain-induced ventricular fibrillation was 40% that of (-)-propranolol.4. Structure-activity relations of beta-receptor blocking drugs are discussed.
D000083:Acetanilides / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001001:Anura; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D010042:Ouabain / Q000037:antagonists & inhibitors; D011433:Propranolol / Q000494:pharmacology*; D011802:Quinidine; D011817:Rabbits; D013565:Sympatholytics / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000188:drug therapy
D000083:Acetanilides; D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D013565:Sympatholytics; D010042:Ouabain; D011433:Propranolol; D011802:Quinidine