ABSTRACT
The intense antifibrillatory and antiarrhythmic actions of GS 015, a derivative of the novel structure series of the 5-(beta-aminoacyl)-3-carbalkoxyamino-iminodibenzyles, are demonstrated on models of myocardial ischaemia: antifibrillatory action on the acute coronary occlusion in the conscious rat (1.0 mg/kg i.v.) and antiarrhythmic action on the two-step coronary ligature in the conscious dog according to Harris (2.0 mg/kg i.v. and 5.0 mg/kg orally). On the strength of the present results it is discussed that GS 015 is first of all suitable for influencing "early arrhythmias" with re-entry mechanism and only in the second line for taking an influence on "late arrhythmias" which arise from the occurrence of ectopic focuses. The substance seems suitable for preventing terminal arrhythmias in patients with ischaemic heart disease as well as for treating arrhythmias in the acute stage of myocardial infarction.
Subject(s)
Anti-Arrhythmia Agents/pharmacology , Arrhythmias, Cardiac/drug therapy , Coronary Disease/complications , Dibenzazepines/pharmacology , Animals , Arrhythmias, Cardiac/etiology , Coronary Circulation/drug effects , Dogs , Male , Rats , Time FactorsABSTRACT
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. A negative inotropic effect appears only at increased doses. Like other antiarrhythmic drugs, GS 015 possesses a limited therapeutic range which should be taken into consideration particularly in case of cardiac insufficiency. But an application seems possible also in patients during the acute stage of myocardial infarction.
Subject(s)
Anti-Arrhythmia Agents/pharmacology , Dibenzazepines/pharmacology , Hemodynamics/drug effects , Anesthesia , Animals , Cats , Coronary Circulation/drug effects , Dogs , Injections, Intravenous , Myocardial Contraction/drug effects , Species SpecificityABSTRACT
The antiarrhythmic action of GS 015 was studied in proportion to its plasma concentrations ascertained in parallel, making use of the model of the two-step coronary ligature in the conscious dog. Blood levels of 1.0 microgram/ml (2 mg/kg i.v.) or of 0.8 microgram/ml (5 mg/kg orally) brought about a complete suppression of ectopic arrhythmias. The limit concentration for this effect is about 0.5 microgram/ml.
