Quinacainol, a new antiarrhythmic with class I antiarrhythmic actions in the rat.
The antiarrhythmic and electrophysiological actions of quinacainol, a new Class I antiarrhythmic, were assessed in rats. Electrophysiological actions of quinacainol were assessed in vivo in terms of drug-induced changes in ECG, responses to left ventricular electrical stimulation, and changes in epicardial intracellular potentials to precisely characterize the electrophysiological effects of this putative subclass Ic antiarrhythmic compound. Antiarrhythmic actions were assessed in conscious rats subjected to occlusion of the LAD coronary artery. Antiarrhythmic actions occurred with 2.0 and 4.0 mg/kg, whereas 8.0 mg/kg was pro-arrhythmic. At doses of 0.5 mg/kg and above quinacainol increased threshold currents for capture and for ventricular fibrillation. Doses of 2.0 mg/kg and above increased ventricular refractoriness. From 1.0 to 8.0 mg/kg, quinacainol reduced dV/dtmax of phase 0 of epicardial action potentials but only 8.0 mg/kg increased action potential duration. The Q-T interval was also increased with the highest dose. Quinacainol dose-relatedly increased P-R interval whereas QRS did not change. Thus the Class I electrophysiological properties of quinacainol over the dose range tested did not fit accurately into a single subclass of the various subclasses of Class I. However, the Class Ic actions seen with 2.0 and 4.0 mg/kg were associated with antiarrhythmic actions.
Howard
P G
PG
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
MacLeod
B A
BA
Walker
M J
MJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000889:Anti-Arrhythmia Agents; D011804:Quinolines; C037907:quinacainol