title: Antiarrhythmic activity of some xanthone derivatives with β1-adrenoceptor affinities in rats.
abstract: A series of aminoalkanolic derivatives of xanthone with high affinity for β1-adrenoceptors was evaluated for antiarrhythmic activity in the model of ischemia-reperfusion in isolated hearts, as well as in barium chloride- and adrenaline-induced model of arrhythmia. In order to better understand biological activity of studied compounds, the influence on β2-adrenoceptors in guinea-pig trachea and vasorelaxant properties in rat aorta were evaluated. Furthermore, due to assessed antioxidant activity, some biochemical studies were also performed. All tested compounds showed prominent antiarrhythmic activity in the model of ventricular arrhythmias associated with coronary artery occlusion and reperfusion. In this experiment the most active was compound MH-97. Whereas, compound MH-82 was the most active in barium- and adrenaline-induced arrhythmia after i.v. or p.o. administration, respectively. These two compounds have higher affinity to β1-adrenoceptors than compound MH-87, thus it suggests that blocking properties of β1-adrenoceptors are involved in the observed antiarrhythmic effects. All studied compounds have revealed antagonistic potency for β2-adrenoceptors in tracheal smooth muscle, however weaker than that of propranolol. None of tested compounds demonstrated antioxidant effect. They also had weak calcium entry blocking activity. The results of this study suggest that new compounds with antiarrhythmic activity might be found in the group of xanthone derivatives.
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland. Electronic address: a.rapacz@uj.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Rapacz
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bednarski
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Szkaradek
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Marona
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology; D001262:Atenolol / Q000494:pharmacology; D017609:Barium Compounds / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004837:Epinephrine / Q000009:adverse effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D011433:Propranolol / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000503:physiopathology; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D044004:Xanthones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D017609:Barium Compounds; D002712:Chlorides; D018342:Receptors, Adrenergic, beta-1; D044004:Xanthones; C024986:barium chloride; D001262:Atenolol; D011433:Propranolol; D004837:Epinephrine
keywords: Antiarrhythmic; Ischemia; Reperfusion; Smooth muscle relaxation; Xanthones; β-Adrenoceptor antagonists