Antiarrhythmic properties of some 1,4-disubstituted piperazine derivatives with α1-adrenoceptor affinities.

Abstract

A series of 1,4-disubstituted piperazine derivatives with α1-adrenolytic properties was evaluated for antiarrhythmic, electrocardiographic and antioxidant activity in vitro and in vivo. Most of them displayed strong antiarrhythmic activity in the adrenaline induced model of arrhythmia and in the rat coronary artery ligation-reperfusion model. Their antiarrhythmic effect is mainly related to α1-adrenolytic properties. Among them one compound showed characteristics similar to quinidine in different arrhythmia models as well as electrocardiogram (ECG) studies which suggests that it possesses not only α1-adrenoceptor blocking properties but also affinity for cardiac Na(+) and K(+) channels, similar to class IA antiarrhythmic agents. Two other compounds revealed some antioxidant effects. Another compound (MH-79) is particularly promising since it displayed a strong antiarrhythmic effect without the influence on ECG record.

• Authors: Monika Kubacka, Szczepan Mogilski, Barbara Filipek, Henryk Marona
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 720 Issue 1-3 Pg. 237-46 (Nov 15 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 24161912 (Publication Type: Journal Article)
• Copyright: © 2013 Published by Elsevier B.V.

Chemical References

• Adrenergic beta-1 Receptor Antagonists
• Anti-Arrhythmia Agents
• Nitrates
• Nitrites
• Piperazines
• Receptors, Adrenergic, beta-1
• Epinephrine

Topics

• Adrenergic beta-1 Receptor Antagonists (pharmacology, therapeutic use)
• Animals
• Anti-Arrhythmia Agents (pharmacology, therapeutic use)
• Arrhythmias, Cardiac (chemically induced, drug therapy)
• Cerebral Cortex (metabolism)
• Epinephrine
• Heart (drug effects, physiology)
• In Vitro Techniques
• Male
• Nitrates (metabolism)
• Nitrites (metabolism)
• Piperazines (pharmacology, therapeutic use)
• Radioligand Assay
• Rats
• Rats, Wistar
• Receptors, Adrenergic, beta-1 (metabolism)