Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adrenergic Antagonists / chemistry
-
Adrenergic Antagonists / pharmacology*
-
Adrenergic Antagonists / therapeutic use
-
Animals
-
Anti-Arrhythmia Agents / chemistry
-
Anti-Arrhythmia Agents / pharmacology*
-
Anti-Arrhythmia Agents / therapeutic use
-
Antioxidants / chemistry
-
Antioxidants / pharmacology*
-
Arrhythmias, Cardiac / chemically induced
-
Arrhythmias, Cardiac / etiology
-
Arrhythmias, Cardiac / prevention & control
-
Barium Compounds / pharmacology
-
Brain / metabolism
-
Cardiac Complexes, Premature / chemically induced
-
Cardiac Complexes, Premature / etiology
-
Cardiac Complexes, Premature / prevention & control
-
Chlorides / pharmacology
-
Drug Design
-
Electrocardiography
-
Heart / drug effects*
-
Heart / physiopathology
-
Heart Rate / drug effects
-
Lipid Peroxidation / drug effects
-
Male
-
Molecular Structure
-
Myocardial Reperfusion Injury / complications
-
Pyrrolidinones / chemistry
-
Pyrrolidinones / pharmacology*
-
Pyrrolidinones / therapeutic use
-
Rats
-
Rats, Wistar
-
Software
-
Tachycardia, Ventricular / etiology
-
Tachycardia, Ventricular / prevention & control
-
Ventricular Fibrillation / chemically induced
-
Ventricular Fibrillation / etiology
-
Ventricular Fibrillation / prevention & control
Substances
-
Adrenergic Antagonists
-
Anti-Arrhythmia Agents
-
Antioxidants
-
Barium Compounds
-
Chlorides
-
Pyrrolidinones
-
barium chloride