aconitine and bucumolol

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.

Topics: Aconitine; Aconitum; Adrenergic beta-Antagonists; Anesthetics, Local; Animals; Anti-Arrhythmia Agents; Anura; Arrhythmias, Cardiac; Coumarins; Dogs; Female; Guinea Pigs; Heart Atria; Heart Rate; Heart Ventricles; In Vitro Techniques; Isoproterenol; Male; Ouabain; Propanolamines; Propranolol; Quinidine; Refractory Period, Electrophysiological; Stereoisomerism; Stimulation, Chemical; Structure-Activity Relationship