Effects of cetirizine on the delayed K+ currents in cardiac cells: comparison with terfenadine
E Carmeliet - British journal of pharmacology, 1998 - Wiley Online Library
E Carmeliet
British journal of pharmacology, 1998•Wiley Online LibraryThe aim of the present experiments was to analyse the effect of the H1‐histamine
antagonist, cetirizine, on the delayed K+ currents in cardiac cells and to compare its effects
with another H1‐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 IKr current in rabbit
ventricular myocytes was depressed and its voltage‐dependence shifted in the negative …
antagonist, cetirizine, on the delayed K+ currents in cardiac cells and to compare its effects
with another H1‐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 IKr current in rabbit
ventricular myocytes was depressed and its voltage‐dependence shifted in the negative …
- The aim of the present experiments was to analyse the effect of the H1‐histamine antagonist, cetirizine, on the delayed K+ currents in cardiac cells and to compare its effects with another H1‐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 IKr current in rabbit ventricular myocytes was depressed and its voltage‐dependence shifted in the negative direction with a V1/2 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 mM cetirizine.
- In rabbit ventricular myocytes the IC50 for block of IKr was 108±8 μM (n=5); in guinea‐pig ventricular myocytes this concentration of cetirizine reduced the rapidly activating component IKr to 49±4.5% (n=5), while the slowly activating IKs was less affected and only inhibited to 79±2.3% (n=5).
- The block of IKr 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 IKr, the IC50 being 96±15 nM (n=6).
- Based on the present results and information in the literature on binding, it was concluded that cetirizine is a relatively selective H1‐histamine receptor antagonist, with minor effects on K+ currents. The IC50 concentration for IKr block in heart cells was 1.000 times higher than the concentrations needed to block H1 histamine receptors. The occurrence of cardiac arrhythmias due to K+ current blockade is therefore unlikely with this drug.
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