Electrophysiological effects of antidepressants on mammalian hearts and crayfish giant axon.
Cardiotoxicity is known to occur in patients with or without preexisting cardiac diseases during treatments with the tricyclic antidepressants, amitriptyline and imipramine. The antiarrhythmic action of tricyclics was also demonstrated in clinical studies and in animal experiments. Bupropion, a novel antidepressant, is being studied in man and to date has been found to be effective and devoid of cardiovascular toxicity. This study was intended to show the direct effect of tricyclic antidepressants on excitable membrane and to compare their potential toxicity with bupropion in isolated tissues. In crayfish giant axon, all antidepressants exhibited local anesthetic-like action by reducing the action potential amplitude and maximal rate of upstroke (dv/dt). The tricyclics slowed spontaneous sinus discharges in rat atrium and prolonged the duration of evoked action potential in guinea pig atrium with a concomitant decrease in dv/dt. A quinidine-like action of the tricyclic agents is displayed in the termination of spontaneous depolarization and the suppression of dv/dt of evoked action potential in canine Purkinje fibers. The membrane depressant action of antidepressants resulted in the reduction of dv/dt and increased membrane refractoriness in both atrial and ventricular tissues; excitation is blocked even when resting membrane potential remained fully polarized. The present results confirmed the direct quinidine-like action on cardic tissues, which is probably related to the antiarrhythmic and/or cardiotoxic manifestation in man and animals. On on excitable tissues studied, tricyclic antidepressants are the most potent in blocking membrane excitation, while bupropion is the least toxic on the molar basis.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D003400:Astacoidea / Q000502:physiology*; D001369:Axons / Q000187:drug effects*; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic