Description
PEPA is a positive allosteric modulator (PAM) of AMPA receptors. It selectively increases glutamate-induced currents in X. laevis oocytes expressing the flop isoforms of the AMPA receptor subunits glutamate receptor 3 (GluR3) and GluR4 over the flip isoforms of these subunits at 200 μM. PEPA (10 mg/kg) decreases the latency to find the platform in the Morris water maze, indicating reversal of memory deficits, in a rat model of memory impairment induced by middle cerebral artery occlusion (MCAO). It decreases freezing time in a contextual fear freezing paradigm in mice when administered at a dose of 30 mg/kg.
Biological Activity
Novel allosteric potentiator of AMPA receptor desensitization. Slows the rate of onset of desensitization and potentiates steady-state equilibrium currents induced by glutamate with subunit (GluR3/4 > GluR1) and splice variant (flop > flip) selectivity. Ameliorates post-ischemic memory impairment in rats following i.v. administration.
Biochem/physiol Actions
2,6-Difluoro-4-[2-(phenylsul-fonyl-amino)-ethyl-thio]-phenoxy-acet-amide is a structurally novel, selective, high affinity AMPA ionotropic glutamate receptor agonist that reduces ischemia-induced performance deficits in rats.
References
[1] Sekiguchi, M., Fleck, M.W., Mayer, M.L., et al. A novel allosteric potentiator of AMPA receptors: 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide. J. Neurosci. 17(15), 5760-5771 (1997).
[2] Sekiguchi, M., Yamada, K., Jin, J., et al. The AMPA receptor allosteric potentiator PEPA ameliorates post-ischemic memory impairment. Neuroreport 12(13), 2947-29950 (2001).
[3] KO ZUSHIDA. Facilitation of extinction learning for contextual fear memory by PEPA: a potentiator of AMPA receptors.[J]. Journal of Neuroscience, 2007, 27 1: 158-166. DOI:
10.1523/JNEUROSCI.3842-06.2007.
