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Effects of cetirizine on the delayed K + currents in cardiac cells: comparison with terfenadine
Author(s) -
Carmeliet Edward
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701879
Subject(s) - terfenadine , cetirizine , chemistry , patch clamp , histamine , histamine h1 receptor , myocyte , antagonist , guinea pig , pharmacology , biophysics , medicine , receptor , biochemistry , biology
The aim of the present experiments was to analyse the effect of the H 1 ‐histamine antagonist, cetirizine, on the delayed K + currents in cardiac cells and to compare its effects with another H 1 ‐histamine antagonist terfenadine, known to possess proarrhythmic effects. Whole cell currents were measured by use of the single electrode patch‐clamp technique in rabbit and guinea‐pig myocytes. The activation relationship for the I Kr current in rabbit ventricular myocytes was depressed and its voltage‐dependence shifted in the negative direction with a V 1/2 value −13.4±2.4 mV under control conditions which changed to −19.1±1.9 mV ( n =4) in the presence of 0.1 m M cetirizine. In rabbit ventricular myocytes the IC 50 for block of I Kr was 108±8 μ M ( n =5); in guinea‐pig ventricular myocytes this concentration of cetirizine reduced the rapidly activating component I Kr to 49±4.5% ( n =5), while the slowly activating I Ks was less affected and only inhibited to 79±2.3% ( n =5). The block of I Kr did not show use‐dependence and the time course of the tail current was not changed, suggesting rested‐state block or fast activated‐state block and no rapid recovery on deactivation. No important difference was found in the activity of the two enantiomers of cetirizine. Terfenadine in comparison was more potent in blocking I Kr , the IC 50 being 96±15 n M ( n =6). Based on the present results and information in the literature on binding, it was concluded that cetirizine is a relatively selective H 1 ‐histamine receptor antagonist, with minor effects on K + currents. The IC 50 concentration for I Kr block in heart cells was 1.000 times higher than the concentrations needed to block H 1 histamine receptors. The occurrence of cardiac arrhythmias due to K + current blockade is therefore unlikely with this drug.