Antiarrhythmic effectiveness of 3-carbalkoxyamino-5-(omega-aminoacyl)-10,11-dihydro-5H-dibenz-[b,f- azepines

• Published in: Pharmazie Vol. 40; no. 12; p. 830
• Main Authors: Kaverina, N V, Senova, Z P, Lyskovzev, V V, Demina, L M, Grizenko, A N, Skoldinov, A P, Femmer, K, Poppe, H, Stark, A, Wunderlich, H
• Format: Journal Article
• Language: German
• Published: Germany 01-12-1985
• Subjects: Animals; Anti-Arrhythmia Agents - chemical synthesis; Anti-Arrhythmia Agents - pharmacology; Anti-Arrhythmia Agents - toxicity; Chemical Phenomena; Chemistry; Dibenzazepines - chemical synthesis; Dibenzazepines - pharmacology; Dibenzazepines - toxicity; In Vitro Techniques; Lethal Dose 50; Myocardial Contraction - drug effects; Rabbits; Rats
• ISSN: 0031-7144

The derivatives of a novel structure series of dibenzazepines dispose of intense antiarrhythmic properties. The relations between structure and effect in comparison with the antiarrhythmically active derivatives of phenothiazine (Ethmozine) are discussed. When substituting the beta-aminopropionyl chain with cyclic residue by means of a dimethylaminoacyl chain there appears a marked antifibrillatory action besides of the intense antiarrhythmic one. The compound 17, the 3-carbethoxyamino-5-dimethylaminoacetyl-dibenzazepine, proved to be the most efficacious compound in the course of the basic screening on two models: action on the effective refractory period in the rabbit's atrium and aconitin-induced arrhythmia in the conscious rat. In comparison with Ethmozin, an antiarrhythmic agent of the phenothiazine type, 17 shows a somewhat lower efficacy in case of i.v. application, but a distinctly intenser one was stated after oral administration. A profound test on the models: two-step coronary ligature in the dog according to Harris and electrofibrillation in the cat's heart, revealed an equally intense antiarrhythmic action but a considerably intenser antifibrillatory one. Therefore the compound 17 (abbreviated designation in the USSR: GS 015 or in the GDR: AWD 19-166) was provided for a thorough pharmacological and toxcological study.