Perampanel inhibition of AMPA receptor currents in cultured hippocampal neurons

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Perampanel is an aryl substituted 2-pyridone AMPA receptor antagonist that was recently approved as a treatment for epilepsy. The drug potently inhibits AMPA receptor responses but the mode of block has not been characterized. Here the action of perampanel on AMPA receptors was investigated by whole-cell voltage-clamp recording in cultured rat hippocampal neurons. Perampanel caused a slow (∼1 s at 3 μM), concentration-dependent inhibition of AMPA receptor currents evoked by AMPA and kainate. The rates of block and unblock of AMPA receptor currents were105M-1s-1and 0.58 s-1, respectively. Perampanel did not affect NMDA receptor currents. The extent of block of non-desensitizing kainate-evoked currents (IC50, 0.56 μM) was similar at all kainate concentrations (3-100 μM), demonstrating a noncompetitive blocking action. Parampanel did not alter the trajectory of AMPA evoked currents indicating that it does not influence AMPA receptor desensitization. Perampanel is a selective negative allosteric AMPA receptor antagonist of high-affinity and slow blocking kinetics.

Original languageEnglish (US)
Article numberA1249
JournalPLoS One
Volume9
Issue number9
DOIs
StatePublished - Sep 17 2014

Fingerprint

AMPA Receptors
Neurons
neurons
receptors
Kainic Acid
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
antagonists
Clamping devices
perampanel
epilepsy
N-Methyl-D-Aspartate Receptors
Inhibitory Concentration 50
Rats
Epilepsy
trajectories
inhibitory concentration 50
Trajectories
Kinetics
kinetics
drugs

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Perampanel inhibition of AMPA receptor currents in cultured hippocampal neurons. / Chen, Chao-Yin; Matt, Lucas; Hell, Johannes W; Rogawski, Michael A.

In: PLoS One, Vol. 9, No. 9, A1249, 17.09.2014.

Research output: Contribution to journalArticle

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