Comparison of the cardiac electrophysiologic effects of NE-10064 with sotalol and E-4031 and their modification by simulated ischaemia

M. A. McIntosh*, M. Tanira, D. Pacini, K. A. Kane

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

The electrophysiologic effects of a new anti-arrhythmic agent NE-10064 were compared with known class III drugs, E-4031 and sotalol, in sheep Purkinje fibres paced at 1 Hz under normal and simulated ischaemic conditions. NE-10064 0.3-3 μM and sotalol 0.3-300 μM prolonged action potential duration at 90% of repolarization (APD90) and effective refractory period (ERP) concentration dependently without affecting APD50 under normal conditions. E-4031 0.3-300 μM prolonged APD50, APD90, and ERP concentration dependently. Percentage increases in APD90 of 20 ± 6, 27 ± 6, and 33 ± 9 were calculated for NE-10064 3 μM, sotalol 300 μM, and E- 4031 1 μM under normal conditions, respectively. The concentration-response curves for all three drugs were shifted to the right under simulated ischaemic conditions. The shift was more marked for NE-10064 and sotalol. Percentage increases in APD90 of 8 ± 5, 13 ± 2, and 23 ± 4 were observed with NE-10064 3 μM, sotalol 300 μM, and E-4031 1 μM during simulated ischaemia. NE-10064 exhibits electrophysiologic characteristics similar to those of known class III agents. Its ability to prolong APD90 under normal conditions may explain its antiarrhythmic action in vivo.

Original languageEnglish
Pages (from-to)653-657
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume23
Issue number4
DOIs
Publication statusPublished - 1994
Externally publishedYes

Keywords

  • Class III antiarrhythmic drugs
  • Electrophysiology
  • NE-10064
  • Simulated ischaemia

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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