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

Neuroreport. 2001 Sep 17;12(13):2947-50. doi: 10.1097/00001756-200109170-00038.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation / drug effects
  • Allosteric Regulation / physiology
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Brain Ischemia / complications
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / physiopathology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / pharmacology*
  • 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 / drug therapy*
  • Memory Disorders / etiology
  • Memory Disorders / physiopathology
  • Nootropic Agents / pharmacology*
  • Phenoxyacetates / pharmacology*
  • Pyrrolidinones / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Receptors, AMPA / drug effects*
  • Receptors, AMPA / metabolism

Substances

  • 4-(2-(phenylsulfonylamino)ethylthio)-2,6-difluorophenoxyacetamide
  • Excitatory Amino Acid Agonists
  • Nootropic Agents
  • Phenoxyacetates
  • Pyrrolidinones
  • Receptors, AMPA
  • aniracetam