Effects of a Novel Cardioprotective Drug, JTV-519, on Membrane Currents of Guinea Pig Ventricular Myocytes

Access this Article

Author(s)

Abstract

We investigated effects of a novel cardioprotective drug, JTV-519 (4-[3-(4-benzylpiperidin-1-yl)propionyl]-7-methoxy-2, 3, 4, 5-tetrahydro-1, 4-benzothiazepine monohydrochloride) on membrane currents of guinea pig ventricular myocytes by whole-cell voltage and current clamp methods. The fast Na<SUP>+</SUP> current (i<SUB>Na</SUB>) was activated by ramp pulses from various holding potentials of -90, -80 or -60 mV to 10 mV with various intervals. At 0.2 Hz, JTV-519 inhibited i<SUB>Na</SUB> in a concentration-dependent manner with an IC<SUB>50</SUB> of approximately 1.2 and 2 μM at the holding potential of -60 and -90 mM, respectively, implicating a voltage-dependent block. Increasing the pulse frequency from 1 to 2 or 3.3 Hz in the presence of 1 μM JTV-519 shortened the time-course and increased the level of i<SUB>Na</SUB> block, indicating a frequency-dependent block. The time-course of i<SUB>Na</SUB> blocking by JTV-519 was slower than that of lidocaine and similar to that of quinidine. Ca<SUP>2+</SUP> current (i<SUB>Ca</SUB>) and the inwardly rectifying K<SUP>+</SUP> current (i<SUB>K1</SUB>) were also inhibited by JTV-519. JTV-519 decreased the duration and the height of the plateau of the action potential. We conclude that JTV-519 has frequency- and voltage-dependent blocking effects on i<SUB>Na</SUB> as well as inhibition of i<SUB>Ca</SUB> and i<SUB>K1</SUB>.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 79(3), 275-281, 1999-03-01

    The Japanese Pharmacological Society

References:  29

Cited by:  2

Codes

  • NII Article ID (NAID)
    10008682637
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4698996
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
Page Top