NEUROPROTECTIVE EFFECT OF YM90K, A NOVEL AMPA KAINATE RECEPTOR ANTAGONIST, IN FOCAL CEREBRAL-ISCHEMIA IN CATS/

We studied the effect of a novel lpha-amino-3-hydroxy-5-methylisoxazol e-4-propionic acid (AMPA)/kainate antagonist, YM90K [6-(1H-imidazol-1- yl)-7-nitro-2, 3(1H, 4H)-quinoxalinedione monohydrochloride], in a foc al cerebral ischemia model using anesthetized cats, Cats were subjecte d 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 occlusi on markedly reduced the volume of ischemic damage (from 2823 +/- 164 m m(3) of the cerebral hemisphere in saline-treated cats to 1737 +/- 305 mm(3) in YM90K-treated cats). No essential differences were observed between YM90K- and saline-treated cats concerning physiological variab les or brain temperature, These results further support the notion tha t the AMPA/kainate receptor plays an important role in the pathogenesi s of focal cerebral ischemia. This evidence for the neuroprotective ef ficacy of YM90K in a gyrencephalic species suggests its therapeutic po tential in the treatment of human stroke.