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  • Title: Effects of dofetilide and EGIS-7229, an antiarrhythmic agent possessing class III, IV, and IB activities, on myocardial refractoriness in hyperkalemia, hypokalemia, and during beta-adrenergic activation in the rabbit papillary muscle in vitro.
    Author: Kovács A, Szénási G.
    Journal: J Pharmacol Sci; 2006 Apr; 100(4):303-9. PubMed ID: 16603803.
    Abstract:
    Lengthening of the effective refractory period (ERP) by EGIS-7229, a class III/Ib/IV drug, and by dofetilide, a selective I(Kr) 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 beta-adrenergic activation. In NK, EGIS-7229 (3 and 10 microM) 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 microM in LK, that is, the effect of EGIS-7229 turned into positive frequency-dependence from 3 to 10 microM. Furthermore, EGIS-7229 lengthened ERP at 10 microM more than dofetilide at 100 nM at 2 Hz stimulation rate (P<0.05). Isoproterenol (30 nM) eliminated the effect of dofetilide on ERP, while EGIS-7229 prolonged ERP during beta-adrenergic activation. In conclusion, efficacy of EGIS-7229 was superior to that of dofetilide in LK and during beta-adrenergic stimulation, suggesting improved antiarrhythmic action for EGIS-7229 under certain conditions in the patient.
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