Electrophysiological effects of GYKI-23 107, a new antiarrhythmic compound, in isolated rabbit and canine cardiac preparations.
The cellular cardiac electrophysiological effects of GYKI-23 107 (1-/2,6-dimethylamino/-2-dimethylaminopropane dihydrochloride), a new investigational antiarrhythmic drug, were studied in rabbit and canine ventricular muscle and Purkinje fibers. For comparison, mexiletine was used. GYKI-23 107, like mexiletine, did not affect the resting membrane potential and slightly reduced the action potential amplitude in both fiber types. The time for repolarization was shortened, but the ratio of effective refractory period to action potential duration was increased by both drugs. The maximum rate of depolarization (Vmax) was depressed by the drugs in a frequency-dependent ("use-dependent") manner. GYKI-23 107 slowed the recovery kinetics of Vmax in the canine ventricular muscle (Tc = 229.9 +/- 5.6 ms; n = 7) and Purkinje fiber (Tc = 149.6 +/- 33.8 ms; n = 7) in the same way as mexiletine. The kinetics of restitution of action potential duration during premature and postmature stimulation were slowed to similar degrees in the presence of both GYKI-23 107 and mexiletine in canine Purkinje fibers. It is concluded that, on the basis of its cardiac cellular electrophysiological effects, GYKI-23 107 can be categorized as a class Ib antiarrhythmic agent.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008801:Mexiletine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D011437:Propylamines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects; D011817:Rabbits
D000889:Anti-Arrhythmia Agents; D011437:Propylamines; D008801:Mexiletine; C052565:GYKI 23107