3,8-Diazabicyclo-[3.2.1]-octane derivatives as analogues of ambasilide, a Class III antiarrhythmic agent

Ambasilide, a representative of Class III antiarrhythmics, was reported to prolong the cardiac action potential duration in the dog, with little or no effect on Ca and Na currents. We synthesised a series of ambasilide analog ues, having the 3,8-diazabicyclo-[3.2.1]-octane moiety instead of the 3,7-d iazabicyclo-[3.3.1]-nonane present in ambasilide. The compounds were tested both in vitro extracellular electrophysiological assays and by the convent ional microelectrode technique. Most of them lengthened the effective refra ctory period (ERP) with no change or slight increase on the impulse conduct ion time (ICT). Similarly some of the tested compounds lengthened the actio n potential duration (APD), a typical Class III feature, without exerting a ny significant effect on the maximal rate of depolarization, therefore appa rently lacking Class I antiarrythmic activity. (C) 2001 Editions scientifiq ues et medicales Elsevier SAS.