[Anti-arrhythmic action of N-(aminoalkylene) derivatives of indoline-2,3-diones and 1,2-benzene-dicarboxiamides].
The aim of study was to modify the structure of indoline-2,3-diones and 1,2-benzenedicarboximides using the pharmacophores of new generation antiarrhythmics and to assess the impact of their structure upon the acute toxicity and antiarrhythmic action. The quaternary derivatives of N-aminoalkylindoline-2,3-diones and N-aminoalkyl-1,2-benzenedicarboximides were synthesized. The acute toxicity of compounds for white mice was tested. Using the calcium chloride- and aconitine-induced arrhythmia models in rats the antiarrhythmic action of derivatives was assessed. It was shown, that the antiarrhythmic action of N-aminoalkyl-1,2-benzenedicarboximides increases by lengthening of alkylene chain from one methylene group to two or by the presence of methanesulfonamide group in benzene ring. These structural changes, especially the presence of methanesulfonamido group, cause the decrease of acute toxicity. Among the N-aminoalkylindoline-2,3-diones the most antiarrhythmic action and minimal toxicity demonstrates the compound containing the bromo-substituted benzene ring.
Stankeviciene
Laimute Marija
LM
Kauno medicinos universiteto Kardiologijos institutas, Sukileliu 17, 3007 Kaunas.
Raiziene
Dalia
D
Vyzas
Vincas
V
Janusiene
Laima
L
D000157:Aconitine; D000475:Alkenes / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D002122:Calcium Chloride; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D000644:Quaternary Ammonium Compounds; D051381:Rats
D000475:Alkenes; D000889:Anti-Arrhythmia Agents; D007211:Indoles; D000644:Quaternary Ammonium Compounds; D002122:Calcium Chloride; D000157:Aconitine