Antiarrhythmic potency of procainamide and N-acetylprocainamide in rabbits.

The antiarrhythmic potency of procainamide (PA) and N-acetylprocainamide (NAPA) has been investigated in rabbits using isolated atrial preparations and ouabain-induced ventricular fibrillation in vivo. At concentrations in the range 3 x 10(-5) to 1 x 10(-3) M, both PA and NAPA decreased the maximum following frequency (MFF) of isolated atria. The dose--response curves were not parallel but at a concentration of 10(-3) M, NAPA had only one tenth of the potency of PA. Threshold level voltage of the atria were increased by PA but NAPA had no significant effect on this parameter. When atria were preincubated with NAPA (1.6 x 10(-4) or 8.0 x 10(-4) M), the dose--response curve for PA on MFF was displaced to the right. Pretreatment of anaesthetised rabbits with either PA (25 mg/kg i.v.) or NAPA (75 mg/kg i.v.) prolonged the time to onset of ouabain-induced ventricular fibrillation. NAPA (25 mg/kg) did not affect the response to PA (25 mg/kg). The data support the view that NAPA is less potent than PA and suggest that, under certain circumstances, NAPA may antagonise the actions of PA.