Cardiovascular and antiarrhythmic effects of the azulene-1-carboxamidine derivative N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3, 8-dimethylazulene-1-carboxamidine.

The azulene-1-carboxamidine derivative N1,N1-Dimethyl-N2-(2- pyridylmethyl)-5-isopropyl-3,8-dimethyl-azulene-1-carboxamidine (CAS 186086-10-2, HNS-32) is a newly synthesized compound. In the present study, direct cardiovascular effects of HNS-32 were assessed using the canine isolated, blood-perfused sinoatrial node, papillary muscle and atrioventricular node preparations, while the antiarrhythmic action was examined using the canine two-stage coronary ligation-induced arrhythmia model. Intracoronary administration of HNS-32 (1-300 micrograms) suppressed the sinus nodal automaticity and ventricular contractile force, while it increased the atrio-His and His-ventricular conduction time as well as the coronary blood flow. Intravenous administration of HNS-32 (5 mg/kg) suppressed the ventricular arrhythmia for approximately 30 min. Since HNS-32 possesses multiple cardiac direct effects which are unique compared with well-established antiarrhythmic drugs, it may become a leading compound in the search for novel antiarrhythmic agents.