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Naunyn Schmiedebergs Arch Pharmacol. 2011 Jan;383(1):13-25. doi: 10.1007/s00210-010-0566-x. Epub 2010 Oct 15.

Antiarrhythmic and antioxidant activity of novel pyrrolidin-2-one derivatives with adrenolytic properties.

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Department of Pharmacodynamic, Laboratory of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.


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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