title: Antiarrhythmic profile and endothelial action of novel decahydroquinoline derivatives.
abstract: We tested antiarrhythmic and endothelial action of novel decahydroquinoline derivatives. Antiarrhythmic activity was analyzed using models of aconitine-, calcium chloride-, and adrenaline-induced arrhythmias in rats. Potency to induce nitric oxide (NO)-dependent coronary vasodilation was assessed in isolated guinea pig heart perfused according to Langendorff technique. Among 15 novel decahydroquinoline derivatives (D1-15), four of them displayed antiarrhythmic activity (D12-D15). D12-D15 compounds were more active in the model of aconitine-induced arrhythmias than in calcium chloride-induced arrhythmias and were inactive in the model of adrenaline-induced arrhythmias. Profile of antiarrhythmic activity of D12-D15 compounds was similar to that of quinidine and procainamide. Interestingly, in the isolated guinea pig heart D14 and D15 (10(-5) M) induced coronary vasodilation, that was mediated by endothelium-derived NO. In conclusion, novel decahydroquinoline derivatives described here (D12-D15) show antiarrhythmic activity typical of antiarrhythmic drugs of class I. Importantly, some of these compounds (D14, D15) release NO from coronary endothelium, which may provide an additional therapeutic benefit.
authors.affiliation: Department of Experimental Pharmacology, Jagiellonian University Medical College, Grzegórzecka 16, PL 31-531 Kraków, Poland.
authors.forename: Valery I
authors.initials: VI
authors.lastname: Kozlovski
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Vdovichenko
authors.forename: Stefan
authors.initials: S
authors.lastname: Chlopicki
authors.forename: Sergey S
authors.initials: SS
authors.lastname: Malchik
authors.forename: Kaldybek D
authors.initials: KD
authors.lastname: Praliyev
authors.forename: Oral T
authors.initials: OT
authors.lastname: Zcilkibayev
mesh_terms: D000157:Aconitine / Q000633:toxicity; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry* / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy; D002122:Calcium Chloride / Q000633:toxicity; D003331:Coronary Vessels / Q000187:drug effects; D004837:Epinephrine / Q000633:toxicity; D005260:Female; D006168:Guinea Pigs; D008297:Male; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D011804:Quinolines; D009569:Nitric Oxide; D002122:Calcium Chloride; D000157:Aconitine; D004837:Epinephrine