Potential antiarrhythmic agents III: 4‐Amino‐n‐[2‐(substituted amino) ethyl]‐2,6‐dimethylbenzamides

4‐Amino‐N‐(2‐morpholinoethyl)‐2,6‐dimethylbenzamide, 4‐amino‐N‐(2‐piperidinoethyl)‐2,6‐dimethylbenzamide, 4‐amino‐N‐[2‐(4‐phenyl‐1‐piperazino)ethyl]‐2,6‐dimethylbenzamide, and 4‐amino‐N‐[2‐(3‐azabicyclo[3.2.2]nonano)ethyl]‐2,6‐dimethylbenzamide were synthesized as potential antiarrhythmic agents. These compounds were found to be capable of prolonging the effective refractory period of the isolated rabbit atria. They also demonstrated prophylactic activity against ouabain. In addition, 4‐amino‐N‐(2‐piperidinoethyl)‐2,6‐dimethylbenzamide was able to terminate ouabain‐induced arrhythmia, and 4‐amino‐N‐(2‐morpholinoethyl)‐2,6‐dimethylbenzamide was active in antagonizing aconitine‐evoked arrhythmia. The four compounds, especially 4‐amino‐N‐[2‐(3‐azabicyclo[3.2.2]nonano)ethyl]‐2,6‐dimethylbenzamide, also showed some degree of local anesthetic activity in the corneal reflex test in rabbits. The pKa and LD₅₀ values of the compounds were determined.