The anti-ischemic effects of CP-060S during pacing-induced ischemia in anesthetized dogs

CP-060S, (-)-(S)-2-1[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 a novel cardioprotective drug which prevents Na+-, Ca2+-overload and has Ca2+ channel blocking activity. We compared the anti-ischemic effects of CP-060S with those of diltiazem, a Ca2+ channel blocker, and R56865, N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazolamine, a Na+-, Ca2+-overload inhibitor, in a canine pacing-induced ischemia model. CP-060S 100 mu g kg(-1) significantly suppressed the pacing-induced ischemic epicardial ST-segment elevation by maximally 75%, while diltiazem 100 mu g kg(-1) suppressed it by maximally 35%. R56865 100 mu g kg(-1) significantly suppressed the ST-segment elevation by maximally 30%. In addition, diltiazem 100 mu g kg(-1) caused synergistic suppression of ST-segment elevation by 70% when administered simultaneously with R56865 100 mu g kg(-1). These results suggest that a Na+-, Ca2+-overload preventive action and a Ca2+ channel blocking action independently contribute to the suppression of the ST-segment elevation. Therefore, CP-060S may suppress pacing-induced ST-segment elevation by a dual action by preventing Na+-, Ca2+-overload and the Ca2+ channel blockade. (C) 1999 Elsevier Science B.V. All rights reserved.