ANTIARRHYTHMIC ACTIVITY OF N,N-DIISOPROPYL-N'-ISOAMYL-N'-DIETHYLAMINOETHYLUREA HYDROCHLORIDE (P-286)

¹ Department of Pharmacology, University of Porto Medical Faculty, Porto, Portugal

The action of P-286 upon several types of experimentally induced cardiac arrhythmias in the anesthetized dog, isolated rabbit heart and isolated atria of the guinea pig is described. In the dog, atrial arrhythmias caused by acetylcholine and aconitine were reverted by P-286, as were ventricular arrhythmias provoked by ouabain; P-286 depressed automaticity and conduction, and had only slight effects on the blood pressure. Electrocardiographic and ballistocardiographic studies on the untreated and ouabain treated dog showed that P-286 in doses effective against disorders of the rhythm did not cause any hemodynamic deterioration.

On the isolated rabbit heart, P-286 depressed heart contractile force, automaticity and conduction, and increased coronary blood flow; the effects on automaticity and conduction were more intense in low K⁺ or high Ca⁺⁺ medium. While aconitine arrhythmias of the isolated guinea-pig atria and ouabain arrhythmias of the rabbit heart were reverted by P-286, the arrhythmias induced by aconitine in the Langendorff preparation were resistant to P-286.

It is suggested that the antiarrhythmic action of P-286 is due to a stabilizing action on the membrane of thie heart muscle cell, related to an alteration in ionic permeability.