Effects of CP-060S on membrane channels in vascular smooth muscle cells from guinea pig.

The newly developed cardioprotective drug, CP-060S, (-)-(S)-2-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-3-[3-[N-methyl-N- [2-(3,4-methylenedioxyphenoxy) ethyl] amino] propyl]-1,3-thiazolidin-4-one hydrogen fumarate, is reported to possess a vasodilating action. Our objective was to examine the effects of CP-060S on the membrane channels in mesenteric arterial cells from guinea pigs, using whole-cell patch-clamp techniques. CP-060S inhibited the Ca2+ channel current in a concentration-dependent manner (ED50 = 1.7 microM at a holding potential of -80 mV and a stimulation frequency of 0.1 Hz). The inhibition was potentiated by a more depolarized holding potential and a higher stimulation frequency. These effects of CP-060S resembled those of diltiazem and gallopamil more than to those of nifedipine; the inhibition was more frequency dependent and less holding-potential dependent than with nifedipine. Higher concentrations of CP-060S also inhibited the delayed K+ channel currents (ED50 = 18 microM). The present observations suggest that CP-060S exhibits the profile of a Ca2+ channel antagonist, similar to that of diltiazem and gallopamil.