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

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.

[Circulatory action and adverse effects of 3-carbethoxyamino-5-dimethylamino-acetyl-iminodibenzyl hydrochloride (Bonnecor, AWD 19-166, GS 015) in the dog and cat].

The haemodynamic and cardiac effects of GS 015, a substance of the series of the novel 5-(dialkyl-aminoacyl)-3-carbalkoxyamino-10,11-dihydro-5H-dibenz-[b ,f]-azepines with very potent antifibrillatory and antiarrhythmic actions, are studied on anaesthetized dogs and cats by means of the catheter technique. The clinical symptoms and the therapeutic range were tested on conscious animals. On the strength of the present results it can be stated that GS 015, given at pharmacodynamically effective doses, does not cause any circulatory side effects.

[Antiarrhythmic action of 3-carbethoxyamino-5-dimethylaminoacetyl-iminodibenzyl hydrochloride (Bonnecor, AWD 19-166, GS -15) on experimental arrhythmia induced by aconitin, ouabain, calcium chloride and barium chloride].

In comparison with detajmium, prajmalium, ajmaline, quinidine, lidocaine, disopyramide, propranolol, and Ethmozin the substance GS 015 is tested on the aconitin-induced arrhythmia of the rat, the auricular fibrillation by aconitin of the dog, the ventricular arrhythmia induced by ouabaine of the dog, the arrhythmia caused by calcium chloride of the rat, and the arrhythmia induced by barium chloride of the rabbit. The particular qualities of effect in the special forms of arrhythmia are discussed in connection with the study of the antiarrhythmic action in case of coronary occlusion, with the increase of the electric fibrillatory threshold, and with the electrophysiologic tests.

[Pharmacology of 1-phenylaminoethylamino-3-(phenoxy)propanol derivatives with beta-adrenergic action].

In the framework of a screening test of new phenoxyalkanolamines the authors tested derivatives with the basic structure Ph1--NHCH2CH2NHCH2CH(OH)CH2--OPh2 for beta-adrenergic blocking activity and sympathicomimetic action on the spontaneously beating atrial preparation from the guinea-pig and on the circulation of the cat. Derivatives with the substituents 2,5-dimethyl, 2-nitro, 3-nitro, 2,6-dimethyl and 2-chloro at Ph1 produced in the atrial preparation a some 3- to 10fold stronger beta 1-adrenergic blockade than propranolol. In in vivo experiments on the cat, all of these compounds had a potent sympathicomimetic effect on the heart, so that they may be classified as specific beta-adrenergic antagonists.

[On the cardiac and hemodynamic side-effects of the beta 2-adrenergic broncholytic agent clenbuterol (Contraspasmin)].

Clenbuterol was tested for cardiac and haemodynamic side-effects by administering cumulative broncholytically efficient doses (continuous infusion) to anaesthetized dogs. The application of a dose of 1.25 micrograms/kg produced increased heart rate (+ 18%), increased maximum pressure-rise rate dp/dt max (+ 44%), increased heart time volume (+ 43%) and decreased total peripheral resistance (- 30%).

[Studies on the circulatory side-effects of 2-[3'-diethylaminopropyl-(1')-carbamoyl]-6,7-dimethoxy-1-thiaiso-chroman-1,1-di oxide ("16-252") (author's transl)].

In view of its application to human beings, the authors tested 3-[3'-diethylaminopropyl-(1')-carbamoyl]-6,7-dimethoxy-1-thiasiochroman-1,1-dio xide ("16-252"), which is a potential antidepressant by its basic neuropharmacological activities, for circulatory side-effects on the rat, the cat and the awake carotid-ligated dog and compared them with those of imipramine. "16-252" differs from imipramine in principle. Whereas imipramine exerts above all a sympathiocomimetic circulatory effect (characterized by tachycardia, increased cardiac output and increased arterial pressure), "16-252" induces bradycardia, a decrease in cardiac output and a reactive increase of the total peripheral resistance.