Effects of calcium antagonist (SM-6586) on cerebral edema and metabolism in forebrain and focal ischemia

Abstract

SM-6586 (SM) is a new derivative of dihydronyridine with a potent calcium blocking activity and an inhibitory activity of Na⁺/H⁺ and Na⁺/Ca⁺⁺ exchange transport. The effects of SM on survival rate, brain edema and metabolites were evaluated using a global ischemic model in spontaneously hypertensive rats (SHR). Further, the effects of SM on the brain water content and T1 relaxation time using NMR were examined in focal cerebral ischemia. Global ischemia was induced by bilateral common carotid artery ligation (BLCL), and focal ischemia was induced by middle cerebral artery occlusion. The survival rate after BLCL was higher in the SM-treated group. The brain water content was lower, the ATP levels were higher and the lactate levels were lower in the SM-treated group as compared to the control group. In the focal ischemia model, the SM-treated group showed a reduction in T1 relaxation time. Also, the brain water content was significantly decreased in the SM-treated group. These results indicate that SM was effective in ameliorating the ischemic insult in both the global and focal cerebral ischemia models.