The AMPA receptor allosteric potentiator PEPA ameliorates post-ischemic memory impairment

PEPA (4-[2-(Phenylsulphonylamino)ethylthio]-2,6-difluorophenoxyacetamide) i s a recently developed allosteric potentiator of AMPA receptors that prefer entially affects flop splice variants. We tested the effects of PEPA on isc hemia-induced memory deficit in rats. Permanent unilateral occlusion of the middle cerebral artery induced severe impairment of performance of rats in the Morris water maze test. Repeated intravenous administration of PEPA (1 , 3, 10 mg/kg/day for 10 days) improved test performance. In contrast, a co rresponding dose of aniracetam, a representative potentiator of AMPA recept or, did not significantly improve test performance. Thus, PEPA is more effe ctive than aniracetam in reversing impaired memory function as assessed by the Morris water maze test; and PEPA may be an effective compound for the t reatment of impaired memory. NeuroReport 12:2947-2950 (C) 2001 Lippincott W illiams & Wilkins.