Comparison of the parasympatholytic activity of ACC‐9358 and disopyramide

1 ACC‐9358 (N‐[(3,5‐di(pyrrolidinylmethyl)‐4‐hydroxy)benzoyl]aniline) is a newly developed analogue of changrolin, an antiarrhythmic agent used in the Peoples Republic of China. Since changrolin and other antiarrhythmic agents exert parasympatholytic activity which may limit their clinical usefulnes...

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Published in:British journal of pharmacology 1986-01, Vol.87 (1), p.87-95
Main Authors: Brown, Barry S., Gorczynski, Richard J., Reynolds, Robert D., Shaffer, Joel E.
Format: Article
Language:English
Subjects:
Animals
Antiarythmic agents
Biological and medical sciences
Carbachol - pharmacology
Cardiovascular system
Disopyramide - pharmacology
Dogs
Dose-Response Relationship, Drug
Female
Guinea Pigs
Heart Rate - drug effects
Ileum - drug effects
In Vitro Techniques
Male
Medical sciences
Methacholine Chloride
Methacholine Compounds - pharmacology
Parasympatholytics - pharmacology
Pharmacology. Drug treatments
Pupil - drug effects
Pyrrolidines - pharmacology
Rats
Vagus Nerve - physiology
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Summary:1 ACC‐9358 (N‐[(3,5‐di(pyrrolidinylmethyl)‐4‐hydroxy)benzoyl]aniline) is a newly developed analogue of changrolin, an antiarrhythmic agent used in the Peoples Republic of China. Since changrolin and other antiarrhythmic agents exert parasympatholytic activity which may limit their clinical usefulness, it was of interest to examine the parasympatholytic effects of ACC‐9358. For comparative purposes we also studied the parasympatholytic activity of disopyramide. 2 In guinea‐pig isolated ileal strips, disopyramide, 3–30 μM, and ACC‐9358, 100–300 μM, competitively antagonized carbachol‐induced contractions with pA2 values of 5.78 and 4.17, respectively. 3 In guinea‐pig isolated right atria, disopyramide 3–30 μM, competitively antagonized methacholine‐induced slowing of spontaneous beating with a pA2 value of 5.99 whereas ACC‐9358, 3–300 μM, produced no significant muscarinic blockade in this preparation. 4 Disopyramide (1.9–15 mg kg−1, i.v.), but not ACC‐9358 (7.5‐1.5 mg kg−1, i.v.), significantly increased rat pupil diameter in vivo. 5 Disopyramide and ACC‐9358 blocked vagal‐induced reductions in heart rate in dogs anaesthetized with pentobarbitone. ED50 values were approximately 0.65 and 11.25 mg kg−1, respectively. 6 We conclude that ACC‐9358 possesses significantly less parasympatholytic activity than disopyramide.
ISSN:0007-1188
1476-5381
DOI:10.1111/j.1476-5381.1986.tb10160.x