Low proarrhythmic potential of citalopram and escitalopram in contrast to haloperidol in an experimental whole-heart model

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• 作者：Gerrit Frommeyer^a ; ^{gerrit.frommeyer@ukmuenster.de" class="auth_mail" title="E-mail the corresponding author} ; Benedict Brü ; cher^a ; Henning von der Ahe^a ; Sven Kaese^a ; Dirk G. Dechering^a ; Simon Kochhä ; user^a ; Harilaos Bogossian^b ; Peter Milberg^a ; Lars Eckardt^a
• 关键词：Citalopram ; Escitalopram ; Haloperidol ; Dispersion of repolarization ; Proarrhythmia ; Sudden cardiac death
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：5 October 2016
• 年：2016
• 卷：788
• 期：Complete
• 页码：192-199
• 全文大小：1179 K

文摘

In several case reports proarrhythmic effects of citalopram and escitalopram have been reported. Systematic analyses on prorarrhythmic effects of these drugs are not yet available.

The aim of the present study was to investigate if application of citalopram, escitalopram or haloperidol provokes polymorphic ventricular tachycardia in a sensitive model of proarrhythmia.

In isolated rabbit hearts monophasic action potentials and ECG showed a significant QT-prolongation after application of citalopram (2 µM: +47 ms, 4 µM: +56ms, P<0.05) accompanied by an increase of action potential duration (APD) but not dispersion of repolarization. Reduced potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EAD) in 2 of 12 hearts but no polymorphic ventricular tachycardia (pVT). Application of escitalopram also increased QT-interval (2 µM: +3 ms, 4 µM: +30 ms, P<0.05) and APD without effects on dispersion. 3 of 10 hearts showed EAD and pVT in 2 of 10 hearts (32 episodes).

The results were compared to 12 rabbits treated with haloperidol which led to an increase in QT-interval (1 µM:+62 ms; 2 µM:+96ms; P<0.01), APD and dispersion (1 µM:+15 ms, 2 µM:+40 ms; P<0.01) and induced EAD in all 12 and pVT in 10 of 12 hearts (152 episodes).

Citalopram and escitalopram demonstrated a rather safe electrophysiologic profile despite significant QT prolongation. In contrast, haloperidol led to significant increase of dispersion of repolarization while this parameter remained stable under the influence of citalopram or escitalopram. These results imply that application of citalopram or escitalopram is not as proarrhythmic as some case reports might suggest while haloperidol is torsadogenic.