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.
Saitoh
M
M
Department of Pharmacology, Yamanashi Medical University, Japan.
Sugiyama
A
A
Hagihara
A
A
Nakazawa
T
T
Hashimoto
K
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D003427:Cross Circulation; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D011725:Pyridines; D014665:Vasodilator Agents; C108264:HNS 32