The AMPA receptor/Na+ channel blocker BIIR 561 CL is protective in a modelof global cerebral ischaemia

In this study, we investigated whether the novel neuroprotective compound d imethyl-{2-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)-phenoxy]ethyl}-amine hydroch loride, BIIR 561 CL, a combined non-competitive antagonist of AMPA receptor s and blocker of voltage-gated Na+ channels, is protective in a rat model o f severe global ischaemia. BIIR 561 CL administered immediately after 10 mi n of ischaemia (occlusion of both carotid arteries plus reduction of arteri al blood pressure to 38-40 mm Hg) significantly reduced hippocampal damage at 4 x 26.8 mg/kg (subcutaneous injections). The competitive AMPA receptor antagonist 2,3-dihydro-6-nitro-7-sulfamoylbenz(F)quinoxaline. NBQX, was use d as a reference compound and was protective at 3 x 30 mg/kg (intraperitone al and/or subcutaneous administration). BIIR 561 CL significantly reduced t he ischaemia-induced premature mortality from 33.6% in the controls to 14.3 %, whereas NBQX treatment had no statistically significant effect. Thus, BIIR 561 CL could be shown to reduce hippocampal damage and premature mortality in a model of severe global ischaemia. A compound with these pro perties might be an interesting candidate for the treatment of disorders re lated to global cerebral ischaemia in man. (C) 2001 Elsevier Science B.V. A ll rights reserved.