VU0477573 is a potent, selective, brain penetrant partial negative allosteric modulator of mGlu5 receptor with Ki of 14 nM, Ca2+ assay IC50 of 32 nM.
VU0477573 shows no activity against the other mGlu receptor subtypes (>10 uM).
VU0477573 exhibits full occupancy of the MPEP site, does not completely inhibit maximal effects of mGlu5 agonists on intracellular calcium mobilization, inositol phosphate (IP) accumulation, or inhibition of synaptic transmission at the hippocampal Schaffer collateral-CA1 synapse.
VU0477573 acts as a full NAM when measuring effects on mGlu5-mediated ERK1/2 phosphorylation.
VU0477573 shows robust efficacy, comparable to the mGlu5 NAM MTEP, in models of anxiolytic activity.
