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

Stefania Villa, Daniela Barlocco, Giorgio Cignarella, Gyula Julius Papp, Beáta Baláti, János Takács, András Varró, András Borosy, Katalin Keserû, Péter Mátyus

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)495-506
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume36
Issue number6
DOIs
Publication statusPublished - Jun 1 2001

    Fingerprint

Keywords

  • Ambasilide
  • Antiarrhythmic activity
  • Diazabicyclo-[3.2.1]-octane

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this