EGIS-7229, the new combined class III antiarrhythmic agent Lack of EAD inducing effect

Tamás Bányász, J. Magyar, A. Varró, Anikó Kovács, Ildikó Gyönös, G. Szénási, P. Nánási

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

EGIS-7229 is a novel antiarrhythmic candidate having multiple mechanisms of action with class III predominance. In this study, the effects of EGIS-7229 and sotalol on action potential duration (APD) and incidence of early afterdepolarizations (EADs) were studied and compared in rabbit papillary muscle by using conventional microelectrode techniques. In control bathing solution, both drugs increased APD in a concentration-dependent manner; however, the prolongation of APD was greater with sotalol than with EGIS-7229 when the same drug concentrations were compared. EAD developed in 3 of the 11 preparations (27%) bathed with a solution containing 3.6 mmol/l CsCl + 2 mmol/l KCl within the first 120 min of superfusion. The addition of 100 μmol/l sotalol to this superfusate increased the incidence of EAD to 83% (10 from 12), whereas the addition of the same concentration of EGIS-7229 prevented the development of EAD in all of the 9 preparations studied. These differences in incidence of EAD are likely attributable to differences in drug-induced increases of APD-50 in the presence of CsCl. Prolongation of APD-90 showed less correlation with incidence of EAD than changes in APD-50. On the basis of these in vitro results, high concentrations of EGIS-7229 cannot be expected to be torsadogenic in vivo-in contrast with sotalol-presumably owing to the combined class III + IV activity of the compound. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)329-333
Number of pages5
JournalGeneral Pharmacology
Volume32
Issue number3
DOIs
Publication statusPublished - Mar 1999

Fingerprint

Action Potentials
Sotalol
Incidence
Pharmaceutical Preparations
Papillary Muscles
Microelectrodes
EGIS 7229
Rabbits
cesium chloride

Keywords

  • Action potential duration
  • Afterdepolarizations
  • Antiarrhythmic drugs
  • Cardiac muscle
  • Electrophysiology

ASJC Scopus subject areas

  • Pharmacology

Cite this

EGIS-7229, the new combined class III antiarrhythmic agent Lack of EAD inducing effect. / Bányász, Tamás; Magyar, J.; Varró, A.; Kovács, Anikó; Gyönös, Ildikó; Szénási, G.; Nánási, P.

In: General Pharmacology, Vol. 32, No. 3, 03.1999, p. 329-333.

Research output: Contribution to journalArticle

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