title: Antiarrhythmic and cardiovascular profiles of the fused indole compound (3aR,12R,12aR,12bS)-12-amino-2,3,3a,4,11,12,12a,12b-octahydro-10-hydrox yisoquino [2,1,8-lma]carbazol-5(1H)-one hydrochloride 1.5 hydrate.
abstract: Antiarrhythmic and cardiovascular profiles of a fused indole compound, (3aR,12R,12aR,12bS)-12-amino-2,3,3a,4,11,12,12a,12b -octahydro- 10-hydroxyisoquino [2,1,8-lma]carbazol-5(1H)-one hydrochloride 1.5 hydrate (RS-2135, CAS 133775-36-7), were investigated in anesthetized dogs. Class I antiarrhythmic agents such as disopyramide, lidocaine, mexiletine and flecainide were used as reference compounds. RS-2135 exerted more potent antiarrhythmic activity than reference compounds against ouabain-induced arrhythmias in dogs. The onset of action was slow, but the duration of action was longer than with the other compounds tested. The agent suppressed the conduction in the atrium, A-V node and ventricle more markedly than the reference compounds. RS-2135, however, did not change blood pressure and heart rate at a dose 5 times the dose for antiarrhythmic activity and decreased cardiac contractility to a lesser extent than the reference compounds.
authors.affiliation: Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Yorikane
authors.forename: H
authors.initials: H
authors.lastname: Mizuno
authors.forename: Y
authors.initials: Y
authors.lastname: Itoh
authors.forename: H
authors.initials: H
authors.lastname: Koike
authors.forename: S
authors.initials: S
authors.lastname: Miyake
authors.forename: H
authors.initials: H
authors.lastname: Shiga
authors.forename: S
authors.initials: S
authors.lastname: Kumakura
authors.forename: M
authors.initials: M
authors.lastname: Fukami
authors.forename: Y
authors.initials: Y
authors.lastname: Shimoji
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control; D002227:Carbazoles / Q000494:pharmacology*; D002725:Chloroform; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005424:Flecainide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology*; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008801:Mexiletine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain
chemical_list: D000889:Anti-Arrhythmia Agents; D002227:Carbazoles; D007546:Isoquinolines; C073517:RS 2135; D008801:Mexiletine; D010042:Ouabain; D002725:Chloroform; D008012:Lidocaine; D004206:Disopyramide; D005424:Flecainide