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lüll A review of HNS-32: a novel azulene-1-carboxamidine derivative with multiple cardiovascular protective actions Tanaka Y; Shigenobu KCardiovasc Drug Rev 2001[Win]; 19 (4): 297-312HNS-32 [N(1),N(1)-dimethyl-N(2)-(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene-1- carboxamidine] (CAS Registry Number: 186086-10-2) is a newly synthesized azulene derivative. Computer simulation showed that its three dimensional structure is similar to that of the class Ib antiarrhythmic drugs, e.g., lidocaine or mexiletine. HNS-32 potently suppressed ventricular arrhythmias induced by ischemia due to coronary ligation and/or ischemia-reperfusion in dogs and rats. In the isolated dog and guinea pig cardiac tissues, HNS-32 had negative inotropic and chronotropic actions, prolonged atrial-His and His-ventricular conduction time and increased coronary blood flow. In the isolated guinea pig ventricular papillary muscle, HNS-32 decreased maximal rate of action potential upstroke (Vmax) and shortened action potential duration (APD). These findings suggest that HNS-32 inhibits inward Na+ and Ca2+ channel currents. In the isolated pig coronary and rabbit conduit arteries, HNS-32 inhibited both Ca2+ channel-dependent and -independent contractions induced by a wide variety of chemical stimuli. HNS-32 is a potent inhibitor of protein kinase C (PKC)-mediated constriction of cerebral arteries. It is likely to block both, Na+ and Ca2+ channels expressed in cardiac and vascular smooth muscles. These multiple ion channel blocking effects are largely responsible for the antiarrhythmic and vasorelaxant actions of HNS-32. This drug may represent a novel approach to the treatment of arrhythmias.|Action Potentials/drug effects[MESH]|Animals[MESH]|Anti-Arrhythmia Agents/chemistry/*pharmacology[MESH]|Calcium Channel Blockers/pharmacology[MESH]|Calcium Channels, L-Type/drug effects[MESH]|Cerebral Arteries/drug effects[MESH]|Coronary Vessels/drug effects[MESH]|Heart Rate/drug effects[MESH]|Myocardial Contraction/drug effects[MESH]|Protein Kinase C/antagonists & inhibitors[MESH]|Pyridines/chemistry/*pharmacology[MESH]|Sodium Channel Blockers/pharmacology[MESH]|Vasodilator Agents/chemistry/*pharmacology[MESH] |