Anti-arrhythmic effect of changrolin combined with nicotinamide in experimental arrhythmia

Changrolin is a new anti-arrhythmic drug. The ED 50 of changrolin in combination with nicotinamide against chloroforminduced ventricular fibrillation in mice was 3.6 mg/kg, as compared with 9.7 mg/kg for changrolin alone. The therapeutic potency of changrolin in combination with nicotinamide was elevated 1.7 times. In beiwutine-induced arrhythmias in rats the anti-arrhythmic efficacy of changrloin+nicotinamide was increased by 69% than changrolin alone. The effect of changrolin and nicotinamide administrated separately or combined on the ventricular fibrillation threshold by electrical stimulation was determined. An elevation of 0.2±0.2 mA was produced bymicotinamide 400 mg/kg iv,2.4±0.8 mA by changrolin 5 mg/kg iv, and 4.1±0.7 mA by a combination of these 2 drugs. The changrilin and changrolin+nicotinamide groups required much more ouabain to cause ventricular premature beats, but there was no significant difference between the two groups. The acute ip LD 50 of changrolin and changrolin+nicotinamide in mice were 0.29 g/kg (0.27-0.32) and 0.29 g/kg (0.27-0.33), respectively.