Proarrhythmic effects of antidepressants and neuroleptic drugs on isolated, spontaneously beating guinea-pig Purkinje fibers

• Published in: European journal of pharmaceutical sciences Vol. 7; no. 2; pp. 113 - 118
• Main Authors: Studenik, Christian, Lemmens-Gruber, Rosa, Heistracher, Peter
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 1999; Elsevier
• Subjects: Action Potentials - drug effects; Animals; Antidepressants; Antidepressive Agents - toxicity; Antipsychotic Agents - toxicity; Arrhythmias, Cardiac - chemically induced; Biological and medical sciences; Calcium Channels - drug effects; Drug toxicity and drugs side effects treatment; Early afterdepolarizations; Female; Guinea Pigs; Guinea-pig Purkinje fibers; In Vitro Techniques; Male; Medical sciences; Neuroleptic drugs; Pharmacology. Drug treatments; Potassium Channels - drug effects; Purkinje Fibers - drug effects; Purkinje Fibers - physiology; Torsades de pointes; Toxicity: cardiovascular system; Neuroleptic drugs; Early afterdepolarizations; Antidepressants; Torsades de pointes; Guinea-pig Purkinje fibers; Arrhythmia; Neuroleptic; Toxicity; Rodentia; Cardiovascular disease; Purkinje fiber; In vitro; Isolated organ; Vertebrata; Mammalia; Guinea pig; Heart disease; Animal; Antidepressant agent; Biological effect; Mechanism of action
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/S0928-0987(98)00013-X

Antidepressants and neuroleptic drugs are sometimes the reason for the occurrence of the polymorphic ventricular arrhythmia torsades de pointes in patients. Therefore, it was of interest to study the actions of some of these drugs such as imipramine, amitriptyline, doxepin, chlorpromazine, trifluoperazine and thioridazine in isolated, spontaneously beating Purkinje fibers of guinea-pig hearts using the intracellular microelectrode technique because experimentally induced early afterdepolarizations (EADs) may be associated with this special type of arrhythmia. If the extracellular K + concentration was 2.7 mM none of these drugs could elicit EADs. For that reason the K + concentration was lowered to 1.35 mM and EADs were evoked by imipramine (2 and 5 μM). Amitriptyline (2 and 5 μM) and doxepin (2 μM) did not induce EADs. Only a concentration of 5 μM doxepin elicited EADs. Among the neuroleptic drugs, chlorpromazine at a concentration of 2 and 5 μM was responsible for the occurrence of EADs as well as thioridazine in the same concentrations. When trifluoperazine (2 and 5 μM) was applied no EADs could be observed. Tetrodotoxin (0.2 μM l −1) abolished thioridazine-induced EADs. Several membrane depolarizing currents may participate in the initiation of these EADs. Our results demonstrate that in guinea-pig Purkinje fibers some tricyclic antidepressants and some neuroleptic drugs are responsible for the rare occurrence of EADs under hypokalemic conditions.