title: 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.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland. Electronic address: mfkuback@cyf-kr.edu.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Kubacka
authors.forename: Szczepan
authors.initials: S
authors.lastname: Mogilski
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.forename: Henryk
authors.initials: H
authors.lastname: Marona
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy; D002540:Cerebral Cortex / Q000378:metabolism; D004837:Epinephrine; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000889:Anti-Arrhythmia Agents; D009566:Nitrates; D009573:Nitrites; D010879:Piperazines; D018342:Receptors, Adrenergic, beta-1; D004837:Epinephrine
keywords: Antiarrhythmic activity; Ischemia; Piperazine derivative; α(1)-adrenoceptor