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A review of HNS-32: a novel azulene-1-carboxamidine derivative with multiple cardiovascular protective actions.

Abstract
HNS-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.
AuthorsY Tanaka, K Shigenobu
JournalCardiovascular drug reviews (Cardiovasc Drug Rev) Vol. 19 Issue 4 Pg. 297-312 ( 2001) ISSN: 0897-5957 [Print] United States
PMID11830749 (Publication Type: Journal Article, Review)
Chemical References
  • Anti-Arrhythmia Agents
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Pyridines
  • Sodium Channel Blockers
  • Vasodilator Agents
  • HNS 32
  • Protein Kinase C
Topics
  • Action Potentials (drug effects)
  • Animals
  • Anti-Arrhythmia Agents (chemistry, pharmacology)
  • Calcium Channel Blockers (pharmacology)
  • Calcium Channels, L-Type (drug effects)
  • Cerebral Arteries (drug effects)
  • Coronary Vessels (drug effects)
  • Heart Rate (drug effects)
  • Myocardial Contraction (drug effects)
  • Protein Kinase C (antagonists & inhibitors)
  • Pyridines (chemistry, pharmacology)
  • Sodium Channel Blockers (pharmacology)
  • Vasodilator Agents (chemistry, pharmacology)

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