Antiarrhythmic profile and endothelial action of novel decahydroquinoline derivatives

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...

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Veröffentlicht in:Polish journal of pharmacology Jg. 56; H. 6; S. 767
Hauptverfasser: Kozlovski, Valery I, Vdovichenko, Vladimir P, Chlopicki, Stefan, Malchik, Sergey S, Praliyev, Kaldybek D, Zcilkibayev, Oral T
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Poland 01.11.2004
Schlagworte:
Aconitine - toxicity
Animals
Anti-Arrhythmia Agents - chemistry
Anti-Arrhythmia Agents - pharmacology
Arrhythmias, Cardiac - chemically induced
Arrhythmias, Cardiac - drug therapy
Calcium Chloride - toxicity
Coronary Vessels - drug effects
Epinephrine - toxicity
Female
Guinea Pigs
Male
Molecular Structure
Nitric Oxide - metabolism
Quinolines - chemistry
Quinolines - pharmacology
Rats
Rats, Wistar
Structure-Activity Relationship
Vasodilation - drug effects
ISSN:1230-6002
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Zusammenfassung: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.
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ISSN:1230-6002