The antiseizure drug perampanel is a subunit-selective negative allosteric modulator of kainate receptors.

ABSTRACT: Perampanel (PMP) is a third generation antiseizure drug reported to be a potent and selective noncompetitive negative allosteric modulator of one sub-family of ionotropic glutamate receptor (iGluR), the α-amino-3-hydroxy-S-methylisoxazole-4-propionic acid receptors (AMPARs). However, the recent structural resolution of AMPARs in complex with PMP revealed that its binding pocket is formed from residues that are largely conserved in two members of another family of iGluRs, the GluK4 and GluK5 kainate receptor (KAR) subunits. We show here that PMP inhibits both recombinant and neuronal KARs, contrary to the previous reports, and that the NAM activity requires GluK5 subunits to be channel constituents. PMP inhibited heteromeric GluK1/GluK5 and GluK2/GluK5 KARs at IC₅₀ values compara

SUBMITTER: Taniguchi S 

PROVIDER: S-EPMC9295835 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature