Antiarrhythmic activity of dextro- and levo-isomers of 5-methyl-8-(2-hydroxy-3-t-butylamino-propoxy) coumarin hydrocholoride (bucumolol), a beta-adrenergic blocking agent, on aconitine-induced atrial and ouabain-induced ventricular arrhythmias in dogs.
The beta-blocking, antiarrhythmic, and local anesthetic effects of the racemic mixture and optical isomers of bucumolol, 5-methyl-8-(2-hydroxy-3-t-butylamino-propoxy) coumarin hydrochloride, were studied in dogs, guinea-pigs and frogs. In blocking the positive chrontropic response to isoproterenol, the levo-isomer of bucumolol was about 40 times more potent in dogs, and 270 times in guinea-pigs than its dextro-isomer and twice as effective in both species as the racemic mixture. In frog sciatic nerves bucumolol was 1/10-1/15 as potent in local anesthetic action as propranolol on a weight basis. Dextro- and levo-isomers and racemic bucumolol neither elevated electrical threshold for propagated impulses nor prolonged the effective refractory period of the dog right atrium. The levo-isomer and racemic bucumolol were capable of suppressing aconitine-induced atrial arrhythmia, while the dextro-isomer was less effective. Both isomers and racemic bucumolol were capable of reversing ventricular arrhythmia caused by ouabain, but the effective dose of the levo-isomer was significantly less than that of the dextro-isomer. The results suggest that both specific beta-blocking activity and non-specific membrane action of bucumolol suppressed experimental arrhythmias in dogs produced by aconitine and ouabain.
D000157:Aconitine; D031841:Aconitum / Q000031:analogs & derivatives; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000779:Anesthetics, Local; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001001:Anura; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000188:drug therapy; D003374:Coumarins / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010042:Ouabain; D011412:Propanolamines; D011433:Propranolol / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013237:Stereoisomerism; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D003374:Coumarins; D011412:Propanolamines; D010042:Ouabain; D011433:Propranolol; D011802:Quinidine; D007545:Isoproterenol; C024221:bucumolol; D000157:Aconitine