The effects of bisaramil on experimental arrhythmias

Antiarrhythmic activity of bisaramil (3-methyl,7-ethyl,9 alpha, 4'-(Cl-benzoyloxy)-3,7-diazabicyclo[3.3.1.]nonane monohydrochloride) was investigated in a variety of experimental arrhythmic models. Bisaramil at the dose range of 0.1-2 mg/kg given i.v. was able to protect against either chemically induced (chloroform, aconitine, adrenaline, ouabain) or coronary-ligation-induced arrhythmias. Bisaramil dose dependently increased fibrillation threshold both in the right auricle and in the right ventricle (ED50 approximately 0.2 mg/kg i.v.) and decreased the susceptibility of the heart to arrhythmias induced by programmed electrostimulation alone or together with local cooling of the heart. Bisaramil given orally (5-20 mg/kg) also showed antiarrhythmic activity with a medium (2-4 h) duration of the action. Therapeutic index of bisaramil was found to be 19.6 (rat); 5.0 (dog) by i.v. administration and 46.5 (rat); 15.5 (dog) by p.o. administration. This means that bisaramil may be given rather safely.