Momir Nesic

University of Szeged, Algyő, Csongrád, Hungary

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Publications (1)2.53 Total impact

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    ABSTRACT: The cellular electrophysiological effect of azimilide (0.1-30 microM) was analyzed in canine ventricular preparations by applying the standard microelectrode and patch-clamp techniques at 37 degrees C. In papillary muscle, the drug prolonged the action potential duration (APD) in a concentration-dependent manner at a cycle length (CL) of 1000 ms. In Purkinje fibers, at the same CL, the concentration-dependent lengthening of the APD was observed in the presence of up to 3 microM azimilide (at 3.0 microM: 24.1+/-4.2%, n=9); at higher drug concentration, no further APD prolongation was observed. Azimilide lengthened APD in a reverse frequency-dependent manner in papillary muscle and Purkinje fibers alike. Azimilide (10 microM) caused a rate-dependent depression in the maximal upstroke velocity of the action potential (V(max)) in papillary muscle. The time and rate constants of the offset and onset kinetics of this V(max) block were 1754+/-267 ms (n=6) and 5.1+/-0.4 beats (n=6), respectively. Azimilide did not prevent the APD shortening effect of 10 microM pinacidil in papillary muscle, suggesting that the drug does not influence the ATP-sensitive K(+) current. Azimilide inhibited the rapid (I(Kr)) and slow component (I(Ks)) of the delayed rectifier K(+) current and the L-type Ca(2+) current (I(Ca)). The estimated EC(50) value of the drug was 0.59 microM for I(Ks), 0.39 microM for I(Kr) and 7.5 microM for I(Ca). The transient outward (I(to)) and the inward rectifier (I(k1)) K(+) currents were not influenced by the drug. It is concluded that the site of action of azimilide is multiple, it inhibits not only K(+) (I(Kr), I(Ks)) currents but, in higher concentrations, it also exerts calcium- and use-dependent sodium channel block.
    Full-text · Article · Jul 2003 · European Journal of Pharmacology

Publication Stats

10 Citations
2.53 Total Impact Points

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  • 2003
    • University of Szeged
      • Department of Pharmacology and Pharmacotherapy
      Algyő, Csongrád, Hungary