Better antiarrhythmics? Development of antiarrhythmic drugs selective for ischaemia-dependent arrhythmias

Autor: Richard A. Wall, David Fedida, Allen I. Bain, Terrance D. Barrett, Eric S. Hayes, Alexander Zolotoy, Bertrand Plouvier, Michael K. Pugsley, Mariah L. Walker, Michael J A Walker, Gregory N. Beatch, Sandro L. Yong
Rok vydání: 1997
Předmět:
Zdroj: Drug Development Research. 42:198-210
ISSN: 1098-2299
0272-4391
Popis: RSD1000 is one example of a series of compounds synthesized by Nortran Pharmaceuticals, Inc., to provide selective protection against arrhythmias due to myocardial ischaemia and so providing better therapeutic indices than existing drugs. RSD1019 is an analogue of RSD1000, whose therapeutic indices are better than those of RSD1000. The antiarrhythmic efficacy of RSD1000 and RSD1019 against ventricular arrhythmias induced by myocardial ischaemia were investigated in rats. Doses providing such antiarrhythmic protection were compared with those having effects on the ECG and on electrical stimulation variables and induction of ventricular arrhythmias; such actions are indices of ionic current blockade in normal myocardium. For RSD1019, additional experiments were performed in rabbits and nonhuman primates to rule out species-specific drug actions. The two compounds were also investigated for their effects on isolated rat hearts and on sodium and potassium currents in isolated rat cardiac myocytes. Analogous studies were performed on potassium currents from transfected potassium channels expressed in human mbryonic kidney cells. Lidocaine was used for comparative purposes in several experiments.
Databáze: OpenAIRE
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