Why the study?
Do novel pyrrolidin-2-one derivatives exhibit antiarrhythmic and antioxidant activity in rat models of arrhythmia?
Do novel pyrrolidin-2-one derivatives exhibit antiarrhythmic and antioxidant activity in rat models of arrhythmia?
Novel pyrrolidin-2-one derivatives, particularly EP-40, show promising antiarrhythmic and antioxidant properties in preclinical rat models.
EP-40 shows promise in rat models; leaves open whether pyrrolidin-2-one derivatives merit clinical antiarrhythmic development.
A series of novel pyrrolidin-2-one derivatives (17 compounds) with adrenolytic properties was evaluated for antiarrhythmic, electrocardiographic and antioxidant activity. Some of them displayed antiarrhythmic activity in barium chloride-induced arrhythmia and in the rat coronary artery ligation-reperfusion model, and slightly decreased the heart rate, prolonged P-Q, Q-T intervals and QRS complex. Among them, compound EP-40 (1-[2-hydroxy-3-[4-[(2-hydroxyphenyl)piperazin-1-yl]propyl]pyrrolidin-2-one showed excellent antiarrhythmic activity. This compound had significantly antioxidant effect, too. The present results suggest that the antiarrhythmic effect of compound EP-40 is related to their adrenolytic and antioxidant properties. A biological activity prediction using the PASS software shows that compound EP-35 and EP-40 can be characterized by antiischemic activity; whereas, compound EP-68, EP-70, EP-71 could be good tachycardia agents.
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Sapa et al. (2010) studied this question.
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