Anti-arrhythmic action of 4'-methyl-7-[2-hydroxy-3-(B-propin-amidoethyl)amino]propoxy}flavone hydrochloride (SIPI-644)

SIPI-644 is a new derivative of 4'-methyl-7-(2-hydroxy-3-isopropyl-amino-propoxy) flavone hydrochloride (SIPI-549). Both were synthesized in our Institute. The acute iv LD50 of SIPI-644 and SIPI-549 in mice were 144 (135-154) and 92 (85-99) mg/kg. respectively. SIPI-644 at iv doses of 9 and 14.6 mg/kg increased the threshold dose of aconitine necessary to induce ventricular premature beats (VP). short ventricular tachycardia (SVT), ventricular tachycardia (VT) and ventricular fibrillation (VF). The anti-arrhythmia effects of SIPI-644 were stronger than that of SIPI-549 and amiodarone. In anesthetized guinea pigs. SIPI-644 at the doses of 10.5 and 14.6 mg/kg iv and amiodarone 16 mg/kg iv increased the dose of ouabain necessary to induce VP. SVT, VT and VF. while SIPI-549 9 mg/kg iv did not show marked effect. In the arrhythmia induced by BaCl2 3 mg/kg iv in rats. 14 0ut of 15 rats of SIPI-644 group recovered to sinus thythm but none in control group (10 rats). SIPI-644 possessed stronger anti-arrhythmic effects than SIPI-549. but weaker than amiodarone. SIPI-644 significantly reduced the fibrillation and mortality induced by iv BaCl2 120 mg/kg in anesthetized rats. In anesthetized dogs. the 0.05 and 0.1 LD50 of SIPI-644 had no influence on SAP, DAP. MAP. LVP. LVEDP. dP/dtmax, t-dP/dtmax and (dP/dt)/P. reduced the HR and prolonged Q-T interval: at the dose of mg/kg iv did not antagonize the positive chronotropic action of isoprenaline. 14.6 incidence of ventricular