title: Comparison of the parasympatholytic activity of ACC-9358 and disopyramide.
abstract: 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. In guinea-pig isolated ileal strips, disopyramide, 3-30 microM, and ACC-9358, 100-300 microM, competitively antagonized carbachol-induced contractions with pA2 values of 5.78 and 4.17, respectively. In guinea-pig isolated right atria, disopyramide 3-30 microM, competitively antagonized methacholine-induced slowing of spontaneous beating with a pA2 value of 5.99 whereas ACC-9358, 3-300 microM, produced no significant muscarinic blockade in this preparation. 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. 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. We conclude that ACC-9358 possesses significantly less parasympatholytic activity than disopyramide.
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004206:Disopyramide / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D008688:Methacholine Compounds; D010276:Parasympatholytics; D011759:Pyrrolidines; D016210:Methacholine Chloride; D002217:Carbachol; C048492:4-hydroxy-N-phenyl-3,5-bis(1-pyrrolidinylmethyl)benzamide; D004206:Disopyramide