Electrophysiologic actions of dibenzepin, a tricyclic antidepressant, on canine Purkinje fibers.
Electrophysiologic effects of dibenzepin, a tricyclic antidepressant drug known experimentally to defibrillate the ventricles, were studied in canine Purkinje fibers with glass microelectrodes. In 11 normally perfused preparations the dose-response curve (10(-8)-10(-5) g/ml) revealed that the threshold concentration of this drug was 10(-7) g/ml, reducing the maximal rate of depolarization (MRD) from 930 to 876 V/s and overshoot from 32 to 30 mV, respectively (p less than 0.05). At 10(-6) g/ml, dibenzepin shortened action potential duration (APD) at 50 and 90% repolarization (APD50, APD90), respectively, from 290 to 248 ms and from 385 to 363 ms (p less than 0.001). At 10(-5) g/ml, it decreased the maximal diastolic potential (MDP) from -92 to -85 mV and further reduced MRD, overshoot and APD50 (p less than 0.01). The membrane responsiveness curve was shifted to more negative potentials, but its normalized curve (h infinity curve) remained unchanged. This drug did not alter slow response action potentials produced by 22 mM K+ and 10(-7) M isoproterenol. In six Purkinje fibers, hypoxia (100% N2) reduced MDP and MRD. Subsequent addition of dibenzepin further decreased MRD and shortened APD50. These results indicate that (a) dibezepin inhibits the fast Na+ current without changing its inactivation kinetics, thus suggesting a class 1 antiarrhythmic action; (b) it does not affect the slow inward current; and (c) the former action appears enhanced during hypoxia, possibly contributing to ventricular defibrillation.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003984:Dibenzazepines / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D010100:Oxygen / Q000502:physiology; D011690:Purkinje Fibers / Q000187:drug effects*
D003984:Dibenzazepines; D010100:Oxygen