Antiarrhythmic properties of some aroxyethylamine derivatives with adrenolytic activity.
A series of aroxyethylamines (1-10) have been previously evaluated for antihypertensive and adrenolytic properties. Of the derivatives tested, four (compounds 4, 7, 8 and 10) displayed significant antihypertensive activity and binding affinities for alpha- and beta-adrenergic receptors. As a continuation of our study, we present here the in vivo and in vitro antiarrhythmic activity of compounds 1-10, as well as their electrocardiographic properties. Only compounds 4, 7, 8 and 10 demonstrated strong antiarrhythmic activity in adrenaline induced arrhythmia after intravenous and oral administration. In addition, compounds 4 and 7 significantly decreased heart rhythm disturbances in arrhythmia induced by coronary artery occlusion and reperfusion. The pharmacological results and receptor binding studies suggest that the antiarrhythmic activity of the compounds tested may be related to their adrenolytic properties. Moreover, the presence of a methoxyphenylpiperazine moiety seems to be required for their pharmacological activity.
Maciag
D
D
Department of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University, Kraków, Poland.
Bednarski
M
M
Filipek
B
B
Pociecha
T
T
Szkaradek
N
N
Marona
H
H
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine; D005021:Ethylamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship
D018674:Adrenergic Antagonists; D000889:Anti-Arrhythmia Agents; D005021:Ethylamines; D004837:Epinephrine