The effects of aconitine, higenamine and coryneine derived from processed aconite, a Sino-Japanese medicine on pulse rate were examined in unanaesthetized mice. The intraperitoneal (i.p.) administration of the water extract (3 mg/kg) of processed aconite produced a bradycardia, like bigeminy, within 15 min which was prolonged for 30 min. Aconitine (30 mu g/kg, i.p.) produced a similar bradycardia. Higenamine induced tachycardia at doses of 30 and 100 mu g/kg, i.p. The aconitine-induced bradycardia was antagonized completely by higenamine (10 mu g/kg, i.p.), isoproterenol (1 mu g/kg, s.c.), or scopolamine (10 mu g/kg. s.c.). The anti-aconitine effect of higenamine was prevented by propranolol (1 mg/kg, i.p.). Centrally administered aconitine (1 and 3 mu g) also induced bradycardia. The aconitine (i.c.v.)-induced bradycardia was prevented by centrally administered atropine (1 mu g, i.c.v.). These results demonstrated that aconitine (i.p.)-induced bradycardia is mainly due to a central muscarinic action. As higenamine has a peripheral beta(1)-adrenergic action, like isoproterenol, the inhibition by higenamine of aconitine-induced bradycardia is due to physiological antagonism.
