The AMPA receptor allosteric potentiator PEPA ameliorates post-ischemic memory impairment.
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.
Sekiguchi
M
M
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
Yamada
K
K
Jin
J
J
Hachitanda
M
M
Murata
Y
Y
Namura
S
S
Kamichi
S
S
Kimura
I
I
Wada
K
K
D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D018697:Nootropic Agents / Q000494:pharmacology*; D010642:Phenoxyacetates / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism
C108189:4-(2-(phenylsulfonylamino)ethylthio)-2,6-difluorophenoxyacetamide; D018690:Excitatory Amino Acid Agonists; D018697:Nootropic Agents; D010642:Phenoxyacetates; D011760:Pyrrolidinones; D018091:Receptors, AMPA; C036466:aniracetam