Palatrigine

BW A256C (5(3)‐amino‐6‐(2,3‐dichlorophenyl)‐2,3(2,5)‐dihydro‐3(5)‐imino‐2‐isopropyl‐1,2,4‐triazine) is a novel class 1 antiarrhythmic agent designed to combine the features of potency with reduced central nervous system penetration.BW A256C reduced the maximum rate of depolarization of guinea‐pig ventricle and dog Purkinje fibresin vitro(EC50, 2.2 × 10−6M and 1.8 × 10−6M, respectively), being significantly more potent than quinidine, lidocaine, disopyramide and flecainide. BW A256C was also more potent than these agents at inhibiting aconitine‐induced arrhythmias in anaesthetized rats; however, unlike these agents, BW A256C was devoid of hypotensive activity at antiarrhythmic doses.In anaesthetized dogs, intravenous administration of BW A256C (0.25‐1 mg kg−1) caused a dose‐dependent suppression of ventricular arrhythmias that occurred on reperfusion of an occluded coronary artery.In conscious dogs, intravenous infusion (total dose, 1.5 mg kg−1) or oral administration of BW A256C (1.25‐5 mg kg−1) caused dose‐dependent suppression of the ventricular ectopic activity that occurred following 20–24 h of permanent coronary artery ligation.In the conscious dog, BW A256C was approximately 7 times more potent and was also longer acting than flecainide.Administration of BW A256C was not associated with any evidence of peripheral or CNS toxicity. However, plasma levels 3–4 times greater than the antiarrhythmic levels were associated with a pro‐arrhythmic activity.