title: Comparison of the cardiac electrophysiologic effects of NE-10064 with sotalol and E-4031 and their modification by simulated ischaemia.
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 microM and sotalol 0.3-300 microM 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 microM 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 microM, sotalol 300 microM, and E-4031 1 microM 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 microM, sotalol 300 microM, and E-4031 1 microM 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.
authors.affiliation: Department of Physiology and Pharmacology, Strathclyde Institute for Drug Research, University of Strathclyde, Glasgow, Scotland.
authors.forename: M A
authors.initials: MA
authors.lastname: McIntosh
authors.forename: M
authors.initials: M
authors.lastname: Tanira
authors.forename: D
authors.initials: D
authors.lastname: Pacini
authors.forename: K A
authors.initials: KA
authors.lastname: Kane
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D006827:Hydantoins; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010879:Piperazines; D010880:Piperidines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D012756:Sheep; D013015:Sotalol / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; C063968:E 4031; C086123:azimilide; D013015:Sotalol