Figure 1. VU0409551 is a potent mGlu₅ PAM in HEK293A-mGlu₅ rat cells and native systems.

(A) Representative raw calcium traces following the addition of 30 μM VU0409551 and the subsequent additions of EC₂₀ and EC₈₀ concentrations of glutamate. (B) VU0409551 potentiates an EC₂₀ concentration of glutamate with a potency of 235 nM in mGlu₅-expressing R10A rat cells (C) VU0409551 shifts the glutamate concentration response curve with a maximum fold shift of 11 at 30 μM (D) VU0409551 did not shift the agonist concentration response curve in mGlu_{1,2,3,4,6,7,8}-expressing cells, displaying its high selectivity for mGlu₅. (E) VU0409551 potentiates glutamate-stimulated ERK1/2 phosphorylation and exhibits robust agonist activity in this assay. (F) VU0409551 potentiates glutamate-induced calcium mobilization in rat cortical astrocytes with a potency of 317 nM and maximum glutamate response of 79.5%, which is blocked by addition of 10 μM of the mGlu₅ antagonist MPEP. Data represent mean ± S.E.M. from 2-4 independent experiments performed in duplicate or triplicate.