The AMPA receptor allosteric potentiator PEPA ameliorates... : NeuroReport (original) (raw)

Learning And Memory

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

Sekiguchi, Masayuki* CA; Yamada, Kazuyuki*; Jin, Jingji2; Hachitanda, Mami2; Murata, Yuji2; Namura, Shobu1; Kamichi, Sally3; Kimura, Ichiro3; Wada, Keiji

Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502; 1Stroke and Brain Protection, Research Institute, and Department of Neurosurgery, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565; 2Department of Pharmacology, Panapharm Laboratories Co., Ltd., 1285 Kurisaki, Uto, Kumamoto 869-0425; 3Department of Cell Biology, School of Human Science, Waseda University, 2-579-15 Mikashima, Tokorozawa, Saitama 359-1192, Japan

CACorresponding Author. *Contributed equally to this work.

Received 23 May 2001; accepted 17 July 2001

Abstract

PEPA (4-[2-(Phenylsulphonylamino)ethylthio]-2,6-difluorophenoxyacetamide) is a recently developed allosteric potentiator of AMPA receptors that preferentially affects flop splice variants. We tested the effects of PEPA on ischemia-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 corresponding dose of aniracetam, a representative potentiator of AMPA receptor, did not significantly improve test performance. Thus, PEPA is more effective than aniracetam in reversing impaired memory function as assessed by the Morris water maze test; and PEPA may be an effective compound for the treatment of impaired memory.