M. Boucher et al., CARDIAC ANTICHOLINERGIC EFFECTS OF PROCAINAMIDE AND ITS N-ACETYLATED METABOLITE - EXPERIMENTAL PHARMACOLOGICAL AND RADIOLIGAND BINDING-STUDIES, Journal of autonomic pharmacology, 18(2), 1998, pp. 83-87
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.