PHARMACOLOGICAL ACTIONS OF KYUSHIN, A DRUG CONTAINING TOAD VENOM - CARDIOTONIC AND ARRHYTHMOGENIC EFFECTS, AND EXCITATORY EFFECT ON RESPIRATION

The cardiotonic and arrhythmogenic effects, and the excitatory effect on respiration of ''Kyushin,'' a drug containing toad venom, were studied in comparison with those of digoxin. In anesthetized rabbits, the maximum rate of rise of left ventricular systolic pressure (max dP/dt) was measured as an index of cardiotonic effect, and the respiratory flow was measured as an index of respiratory function. Intraduodenal (i.d.) administration of 80 mg/kg ''Kyushin'' produced a cardiotonic effect and an excitatory effect on respiration, but i.d. administration of 16 mg/kg digoxin produced only a cardiotonic effect, and conversely inhibited respiration. In anesthetized open-chest guinea pigs, myocardial contractile force was measured as an index of cardiotonic effect and the arrhythmogenic effect was evaluated from the appearance of arrhythmic myocardial contraction. By i.d. administration of a 20% ethanol suspension or solution, ''Kyushin'' and digoxin showed a cardiotonic activity with doses higher than 40 mg/kg and 0.25 mg/kg, respectively. The arrhythmogenic doses of ''Kyushin'' and digoxin by i.d. administration were 2560 mg/kg and 2 mg/kg, respectively, suggesting that the safety margin of ''Kyushin'' is broader than that of digoxin.