CARDIAC ANTICHOLINERGIC EFFECTS OF PROCAINAMIDE AND ITS N-ACETYLATED METABOLITE - EXPERIMENTAL PHARMACOLOGICAL AND RADIOLIGAND BINDING-STUDIES

1 The cardiac anticholinergic effects of procainamide (1 mg kg(-1) min (-1)) and its N-acetylated metabolite (NAPA) at equimolar dose (1.16 m g kg(-1) min(-1)) were studied using in vivo experimental pharmacologi cal and in vitro radioligand binding studies. 2 Procainamide and NAPA progressively reduced vagal stimulation-induced bradycardia in chloral ose-anaesthetized dogs. As indicated by the ED50, the vagolytic activi ty of NAPA is 1.5-2.0 times weaker than that of procainamide. Both dru gs increased heart rate, with lowering of mean blood pressure during t he second part of procainamide infusion, but not during NAPA infusion. 3 Binding studies on rat heart membranes yielded K-i values that were 1.5 times higher for NAPA than for procainamide. 4 These results show that NAPA exerts a weaker cardiac vagolytic action than procainamide, which is probably linked to a lower ability to bind to cardiac muscar inic receptors.