Antiarrhythmic activity of new 2-methoxyphenylpiperazine xanthone derivatives after ischemia/reperfusion in rats.
BACKGROUND
We have previously shown significant prophylactic and therapeutic antiarrhythmic activity in adrenaline-induced arrhythmia, as well as α1-adrenolytic properties of new derivatives of xanthone. Herein, we investigated their antiarrhythmic activity in the model of ischemia/reperfusion in isolated hearts. Furthermore, we assessed antioxidant activity in biochemical studies.


METHODS
Antiarrhythmic activity in the model of ischemia/reperfusion in isolated perfused hearts was performed according to the Langendorff technique. Antioxidant activity was measured by lipid peroxidation level in tissue homogenate and in the FRAP assay.


RESULTS
All studied compounds (MH-94, MH-99 and MH-105) showed significant antiarrhythmic activity in the model of ventricular arrhythmias associated with coronary artery occlusion and reperfusion. However, they did not demonstrate antioxidant effect, probably, because of the lack of free hydroxyl group(s) at a key position in the xanthone scaffold.


CONCLUSIONS
The present study provides evidences for antiarrhythmic activity of some 2-methoxyphenylpiperazine derivatives of xanthone.
Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland. Electronic address: a.rapacz@uj.edu.pl.
Anna
A
Rapacz
Department of Pharmacological Screening, Jagiellonian University Medical College, Kraków, Poland.
Jacek
J
Sapa
Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
Karolina
K
Pytka
Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
Magdalena
M
Dudek
Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
Barbara
B
Filipek
Department of Bioorganic Chemistry, Jagiellonian University Medical College, Kraków, Poland.
Natalia
N
Szkaradek
Department of Bioorganic Chemistry, Jagiellonian University Medical College, Kraków, Poland.
Henryk
H
Marona
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000188:drug therapy; D009206:Myocardium / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D044004:Xanthones / Q000494:pharmacology / Q000627:therapeutic use*
C000610387:4-(2-acetoxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one; C000610386:4-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one; C000610385:4-(3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one; D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D010879:Piperazines; D044004:Xanthones
Antiarrhythmic; Ischemia/reperfusion; Piperazine derivatives; Xanthone derivatives