VU0422288

VU0422288 (ML396) is a positive allosteric modulator of group III mGluRs. VU0422288 inhibits mGluRs with EC₅₀s of 125 nM, 146 nM, and 108 nM for mGluR4, mGluR7, and mGluR8, respectively in calcium mobilization assays. VU0422288 reverses deficits in contextual fear memory, social recognition, and apneas in Rett syndrome (RTT) model mice^[1][2]. In Vitro:VU0422288 (1 μM; 5 min) enhances 30 μM LSP4-2022-induced reductions in the field excitatory postsynaptic potentials (fEPSPs) slope on Coronal slices containing the hippocampus^[1].
VU0422288 (1 μM; 10 min) can not alter the fEPSP slopes alone, indicating that mGlu7 is not tonically active in Mecp2^-/y slices under stimulation conditions^[2].
In Vivo:VU0422288 (30 mg/kg; i.p.; once daily for 17 days) rescues synaptic plasticity defects and learning and memory phenotypes, reduces the number of apneas in Mecp2^+/- mice, while VU0422288 has no effect in Mecp2^+/+ animals^[2].
VU0422288 (10 mg/kg; i.p.; single dose) exhibis a plasma/brain partitioning coefficient of 1.67 in adult male Sprague-Dawley rats, with predicted unbound brain concentration of about 40 nM^[2].