Delayed treatment with YM90K, an AMPA receptor antagonist, protects against ischaemic damage after middle cerebral artery occlusion in rats

The neuroprotective effect of an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist YM90K [6-(1H-imidazol-1-yl)-7-nitro-2 ,3( 1H,4H)-quinoxalinedione monohydrochloride] has been examined in a rat m iddle cerebral artery occlusion model. Intravenous infusion of YM90K (2.5-20 mg kg(-1) h(-1) for 4 h) starting imm ediately after occlusion of the middle cerebral artery significantly reduce d the cortical infarct volume 24 h after occlusion compared with the contro l group. The protection at the highest dose was 39% (P < 0.05). Similar pro tective effects were observed when YM90K (20 mg kg(-1) h(-1) for 4 h) was d elayed up to 2 h after middle cerebral artery occlusion (45% reduction, P < 0.05). CNS1102 [N-(1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine hydro chloride], a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonis t, also reduced the cortical infarct volume when 1.13 mg kg(-1) was adminis tered by intravenous bolus injection immediately after middle cerebral arte ry occlusion, followed by intravenous infusion at 0.785 mg kg(-1) h(-1) for 4 h (35% reduction, P < 0.05). This neuroprotective effect was not observe d when administration was delayed Ih after middle cerebral artery occlusion . These results suggest that AMPA receptors might play a more important role than NMDA receptors in the late development of neuronal cell damage after f ocal cerebral ischaemia and that AMPA receptor blockade would be one benefi cial strategy in treating acute stroke.