Neuroprotective effect of YM90K, a novel AMPA/kainate receptor antagonist, in focal cerebral ischemia in cats

Abstract

We studied the effect of a novel α-amino-3-hydroxy-5-methylisoxazole- 4-propionic acid (AMPA)/kainate antagonist, YM90K [6-(1H-imidazol-1-yl)-7- nitro-2, 3(1H, 4H)-quinoxalinedione monohydrochloride], in a focal cerebral ischemia model using anesthetized cats. Cats were subjected to permanent occlusion of the middle cerebral artery (MCA) for 6 h, then killed and examined histologically. The amount of ischemic damage was assessed in 12 stereotaxic coronal sections. Treatment with YM90K (i.v. infusion of 0.5 mg/5 ml/kg/h) starting 10 min after MCA occlusion markedly reduced the volume of ischemic damage (from 2823 ± 164 mm3 of the cerebral hemisphere in saline- treated cats to 1737 ± 305 mm3 in YM90K-treated cats). No essential differences were observed between YM90K- and saline-treated cats concerning physiological variables or brain temperature. These results further support the notion that the AMPA/kainate receptor plays an important role in the pathogenesis of focal cerebral ischemia. This evidence for the neuroprotective efficacy of YM90K in a gyrencephalic species suggests its therapeutic potential in the treatment of human stroke.