Effects of nipradilol (K-351) on the electrophysiological properties of canine cardiac tissues: comparison with propranolol and sotalol.
The electrophysiological effects of K-351 (0.3-300 microM), a new beta-adrenoceptor blocking drug, on canine Purkinje and ventricular muscle fibers were examined and compared with those of propranolol (0.3-30 microM) and sotalol (3-300 microM) using standard microelectrode techniques. K-351 and propranolol dose dependently reduced the maximum upstroke velocity of phase 0 and action potential amplitude in both cardiac tissues. Action potential durations (APD) of Purkinje fibers were shortened by both propranolol and K-351 but prolonged by sotalol. However, in ventricular muscle fibers K-351 and sotalol significantly prolonged APD and effective refractory periods which contrasted with the unchanged APD after propranolol. These results suggest that K-351 is a beta-blocking drug possessing a membrane stabilizing action (class I antiarrhythmic properties) and in ventricular muscles it can also exert an APD-prolonging effect (class III antiarrhythmic properties).
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000502:physiology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013015:Sotalol / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; D011433:Propranolol; D013015:Sotalol; C036089:nipradilol