KC-764

KC-764, developed as a cyclo-oxygenase inhibitor, was administered to gerbils in a dose of 10 mg/kg, i.p., before subjecting them to 5-minute bilateral forebrain ischemia in order to determine whether it would have any protective effects. No post-ischemic hyperthermia (over 39 degrees C for 120 min) was observed in the KC-764 group. Behavior recovery time after ischemia was 11.4 +/- 2.8 minutes in the KC-764 group versus 87.3 +/- 13.4 minutes in the control group (p < 0.05). Delayed neuronal death (DND) in the CA1 region of the hippocampus was inhibited in the KC-764 group, but when the KC-764-treated animals were exposed to hyperthermia, the degree of DND was the same as in the control group. EEG voltage recovery time in the CA1 region of the hippocampus was almost the same in the control group, the KC-764 group, and the KC-764-plus-hyperthermia (HT) group. Although tissue blood flow measurements in the CA1 region of the hippocampus showed post-ischemic hypoperfusion (81 +/- 18% of the pre-ischemic level at 60 minutes), it was prevented in the KC-764 group (102 +/- 21%) (p < 0.05) and the KC-764-plus-HT group (96 +/- 28%). There was a tremendous increase in PGD2 (1461.4 +/- 863.4 p mol/g) and PGF2 alpha (219.6 +/- 104.2 p mol/g) in the forebrain after 5 minutes of reflow, but this increase in prostaglandin levels was inhibited (p < 0.05) in the KC-764 group.(ABSTRACT TRUNCATED AT 250 WORDS)