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.
Ohya
Y
Y
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Adachi
N
N
Setoguchi
M
M
Abe
I
I
Fujishima
M
M
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
C104781:CP 060S; D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; D013844:Thiazoles; D053778:Thiazolidines