Effects of Dofetilide and EGIS-7229, an Antiarrhythmic Agent Possessing Class III, IV, and IB Activities, on Myocardial Refractoriness in Hyperkalemia, Hypokalemia, and During β-Adrenergic Activation in the Rabbit Papillary Muscle In Vitro

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Lengthening of the effective refractory period (ERP) by EGIS-7229, a class III/Ib/IV drug, and by dofetilide, a selective I<sub>Kr</sub> blocker, was compared in normokalemia (NK), hypokalemia (LK), and hyperkalemia (HK) in right ventricular papillary muscles of rabbits paced at 0.5, 1, and 2 Hz, in vitro, and also during β-adrenergic activation. In NK, EGIS-7229 (3 and 10 μM) and dofetilide (30 and 100 nM) similarly lengthened ERP in a steeply reverse frequency-dependent manner. The two compounds produced smaller ERP prolongations at 0.5 Hz in HK and LK, so rate-dependence of ERP changes decreased. EGIS-7229 lengthened ERP more at 2 Hz than at 0.5 Hz at 10 μM in LK, that is, the effect of EGIS-7229 turned into positive frequency-dependence from 3 to 10 μM. Furthermore, EGIS-7229 lengthened ERP at 10 μM more than dofetilide at 100 nM at 2 Hz stimulation rate (<i>P</i><0.05). Isoproterenol (30 nM) eliminated the effect of dofetilide on ERP, while EGIS-7229 prolonged ERP during β-adrenergic activation. In conclusion, efficacy of EGIS-7229 was superior to that of dofetilide in LK and during β-adrenergic stimulation, suggesting improved antiarrhythmic action for EGIS-7229 under certain conditions in the patient.<br>

収録刊行物

  • Journal of pharmacological sciences  

    Journal of pharmacological sciences 100(4), 303-309, 2006-04-20 

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10018240016
  • NII書誌ID(NCID)
    AA11806667
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13478613
  • NDL 記事登録ID
    7884988
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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