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1.
Neuroreport ; 12(13): 2947-50, 2001 Sep 17.
Article in English | MEDLINE | ID: mdl-11588608

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.


Subject(s)
Brain Ischemia/drug therapy , Brain/drug effects , Excitatory Amino Acid Agonists/pharmacology , Memory Disorders/drug therapy , Nootropic Agents/pharmacology , Phenoxyacetates/pharmacology , Receptors, AMPA/drug effects , Allosteric Regulation/drug effects , Allosteric Regulation/physiology , Animals , Brain/metabolism , Brain/physiopathology , Brain Ischemia/complications , Brain Ischemia/physiopathology , Dose-Response Relationship, Drug , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/physiopathology , Male , Maze Learning/drug effects , Maze Learning/physiology , Memory Disorders/etiology , Memory Disorders/physiopathology , Pyrrolidinones/pharmacology , Rats , Rats, Inbred SHR , Receptors, AMPA/metabolism
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