Antiarrhythmic activity of some N-alkylbispidinebenzamides.
A series of aromatic ring substituted bispidinebenzamides, 2--10, was prepared by condensation of N-methyl- or N-n-butylbispidine with the appropriate acid chlorides. These compounds were initially evaluated in mice for acute toxicity and for their ability to protect against chloroform-induced ventricular fibrillation. All compounds had significant activity, which was optimized in 2, 3, and 5. These last compounds had potencies and LD50/ED50 ratios comparable to those of a standard antiarrhythmic, disopyramide. However, their potencies in increasing the effective refactory period in isolated rabbit atria were considerably less than that of disopyramide.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis*; D001549:Benzamides / Q000138:chemical synthesis / Q000494:pharmacology*; D004206:Disopyramide / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D011817:Rabbits; D014693:Ventricular Fibrillation / Q000517:prevention & control
D000889:Anti-Arrhythmia Agents; D001549:Benzamides; D004206:Disopyramide