J. Kimura et al., Effects of a novel cardioprotective drug, JTV-519, on membrane currents ofguinea pig ventricular myocytes, JPN J PHARM, 79(3), 1999, pp. 275-281
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-benzothia
zepine monohydrochloride) on membrane currents of guinea pig ventricular my
ocytes by whole-cell voltage and current clamp methods. The fast Na current
(i(Na)) was activated by ramp pulses from various holding potentials of -9
0, -80 or -60 mV to 10 mV with various intervals. At 0.2 Hz, JTV-519 inhibi
ted iNa in a concentration-dependent manner with an IC50 of approximately 1
.2 and 2 mu M at the holding potential of -60 and -90 mM, respectively, imp
licating a voltage-dependent block. Increasing the pulse frequency from 1 t
o 2 or 3.3 Hz in the presence of 1 mu M JTV-519 shortened the time-course a
nd increased the level of iNa block, indicating a frequency-dependent block
. The time-course of i(Na) blocking by JTV-519 was slower than that of lido
caine and similar to that of quinidine. Ca2+ current (i(Ca)) and the inward
ly rectifying K+ current (i(K1)) were also inhibited by JTV-519. JTV-519 de
creased the duration and the height of the plateau of the action potential.
We conclude that JTV-519 has frequency- and voltage-dependent blocking eff
ects on i(Na) as well as inhibition of i(Ca) and i(K1).