PHARMACOLOGY AND CLINICAL USE OF A NEW GROUP OF ANTIARRHYTHMIC DRUGS - DERIVATIVES OF TRICYCLIC NITROGEN-CONTAINING SYSTEMS

This paper is concerned with a new group of antiarrhythmic drugs: derivatives of phenothiazine and dibenzazepine which belong to tricyclic nitrogen-containing systems. It has been discovered that the transition from ω-aminoalkyl to ω-aminoacyl phenothiazine derivatives results in a decrease in psychotropic activity and an increase in cardiovascular, particularly antiarrhythmic, action. Based on structural and antiarrhythmic activity studies, the new and effective drugs ethmozine, ethacizine and bonnecor have been selected and extensively studied. Data on spectra and mechanisms of their action, obtained in different arrhythmia models, have been confirmed by clinical studies. Correlation between pharmacological properties and electrophysiological mechanisms, and differences in action of the drugs studied on brain and heart plasma membrane receptors may serve as a starting point for the further directed search for new antiarrhythmic drugs among tricyclic nitrogen-containing structures. © 1992 The Italian Pharmacological Society.