C. Studenik et al., Proarrhythmic effects of antidepressants and neuroleptic drugs on isolated, spontaneously beating guinea-pig Purkinje fibers, EUR J PH SC, 7(2), 1999, pp. 113-118
Antidepressants and neuroleptic drugs are sometimes the reason for the occu
rrence of the polymorphic ventricular arrhythmia torsades de pointes in pat
ients. Therefore, it was of interest to study the actions of some of these
drugs such as imipramine, amitriptyline, doxepin, chlorpromazine, trifluope
razine and thioridazine in isolated, spontaneously beating Purkinje fibers
of guinea-pig hearts using the intracellular microelectrode technique becau
se experimentally induced early afterdepolarizations (EADs) may be associat
ed with this special type of arrhythmia. If the extracellular K+ concentrat
ion 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 mu M). Amitriptyline (2 and 5 mu M) and doxepin (2 mu M) did not in
duce EADs. Only a concentration of 5 mu M doxepin elicited EADs. Among the
neuroleptic drugs, chlorpromazine at a concentration of 2 and 5 mu M was re
sponsible for the occurrence of EADs as well as thioridazine in the same co
ncentrations. When trifluoperazine (2 and 5 mu M) was applied no EADs could
be observed. Tetrodotoxin (0.21 mu M) abolished thiorictazine-induced EADs
. Several membrane depolarizing currents may participate in the initiation
of these EADs. Our results demonstrate that in guinea-pig Purkinje fibers s
ome tricyclic antidepressants and some neuroleptic drugs are responsible fo
r the rare occurrence of EADs under hypokalemic conditions. (C) 1998 Elsevi
er Science B.V. All rights reserved.