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Negative Chronotropic Effects of Class I Antiarrhythmic Drugs on Guinea Pig Right Atria: Correlation with L-Type Ca 2+ Channel Blockade

Author

Listed:
  • Haruhito Hiiro

    (Department of Pharmacology, Faculty of Pharmacological Science, Toho University, Funabashi 274-8510, Japan)

  • Kentaro Otsuka

    (Department of Pharmacology, Faculty of Pharmacological Science, Toho University, Funabashi 274-8510, Japan)

  • Shogo Hamaguchi

    (Department of Pharmacology, Faculty of Pharmacological Science, Toho University, Funabashi 274-8510, Japan)

  • Iyuki Namekata

    (Department of Pharmacology, Faculty of Pharmacological Science, Toho University, Funabashi 274-8510, Japan)

  • Hikaru Tanaka

    (Department of Pharmacology, Faculty of Pharmacological Science, Toho University, Funabashi 274-8510, Japan)

Abstract

The negative chronotropic effects of eight Vaughan Williams Class I antiarrhythmic drugs were examined in guinea pig right atrial tissue preparations. The drugs decreased the spontaneous beating rate at concentrations overlapping with their therapeutic blood levels. Cibenzoline, aprindine, flecainide, and propafenone showed stronger effects; 10 µM of each drug decreased the beating rate to about 75% of initial values. Disopyramide, mexiletine, pilsicainide, and ranolazine showed weaker effects; 10 µM of each drug decreased the beating rate to about 90% of initial values. The potency of drugs correlated with the reported IC 50 values to block the L-type Ca 2+ channel current rather than the Na + and K + channel currents. The reported IC 50 values for the blockade of the hyperpolarization-activated inward current (If) and the Na + -Ca 2+ exchanger current were much higher than those for the blockade of the L-type Ca 2+ channel current. These results indicate that the negative chronotropic effects of Class I antiarrhythmic drugs can be largely explained by their blockade of the L-type Ca 2+ channel.

Suggested Citation

  • Haruhito Hiiro & Kentaro Otsuka & Shogo Hamaguchi & Iyuki Namekata & Hikaru Tanaka, 2023. "Negative Chronotropic Effects of Class I Antiarrhythmic Drugs on Guinea Pig Right Atria: Correlation with L-Type Ca 2+ Channel Blockade," J, MDPI, vol. 6(1), pages 1-11, February.
    • Handle: RePEc:gam:jjopen:v:6:y:2023:i:1:p:8-114:d:1065807
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