title: A comparative study on the antiarrhythmic activity and acute toxicity of quinidine and four new analogs in mice.
abstract: We have compared the ED50 value for antiarrhythmic activity and the acute toxicities in mice of quinidine and 4 recently synthesized analogs. For the ED50 studies, groups of mice were treated intravenously with equally spaced logarithmic doses of 6'-methoxycinchonine (quinidine), 6'-hydroxycinchonine (cupreidine), 6'-isovaleryloxycinchonine, 6'-acetyloxycinchonine and 6'-benzoyloxycinchonine. For the actue toxicity studies, mice were treated intraperitoneally with quinidine and the 4 analogs. Mice were observed over a 24-h period, and thereafter for each additional 24-h period for a total of 120 h. Tests for parallelism of acute toxicity indicated that with the exception of the 6'-isovaleryloxy derivative the drug treatment regression lines were parallel to that of quinidine (P >  0.05). The results indicated decreases of 50% (843 mumol/kg), 52% (857 mumol/kg), and 61% (910 mumol/kg) in the acute toxicities of the 6'-acetyloxy, 6'-hydroxy,  and 6'-benzoyloxycinchonine, respectively. The 6'-acetyloxy (18.5 mumol/kg) and 6'-benzoyloxy (14.6 mumol/kg) derivatives had significantly lower ED50 values than quinidine (60.1 mumol/kg). The results suggest that the 6'-acetyloxy and 6'-benzoyloxy derivatives may have much greater antiarrhythmic effectiveness than quinidine.
mesh_terms: D000157:Aconitine / Q000037:antagonists & inhibitors; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011802:Quinidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D011802:Quinidine; D000157:Aconitine