European Journal of Medicinal Chemistry p. 495 - 506 (2001)
Update date:2022-09-26
Topics:
Villa, Stefania
Barlocco, Daniela
Cignarella, Giorgio
Papp, Gyula Julius
Balati, Beata
Takacs, Janos
Varro, Andras
Borosy, Andras
Keseru, Katalin
Matyus, Peter
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 analogues, having the 3,8-diazabicyclo-[3.2.1]-octane moiety instead of the 3,7-diazabicyclo-[3.3.1]-nonane present in ambasilide. The compounds were tested both in vitro extracellular electrophysiological assays and by the conventional microelectrode technique. Most of them lengthened the effective refractory period (ERP) with no change or slight increase on the impulse conduction time (ICT). Similarly some of the tested compounds lengthened the action potential duration (APD), a typical Class III feature, without exerting any significant effect on the maximal rate of depolarization, therefore apparently lacking Class I antiarrythmic activity.
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