mGluR8 Modulator

O-Phospho-L-serine is the immediate precursor to L-cystein in the serine synthesis pathway, and an agonist at the group III mGluR receptors (mGluR4, mGluR6, mGluR7, and mGluR8); O-Phospho-L-serine also acts as a weak antagonist for mGluR1 and a potent antagonist for mGluR2.

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.

VU6081679 is an orally active positive allosteric modulator of mGlu8 with blood-brain barrier permeability. VU6081679 binds to the extracellular allosteric pocket at the TM6/TM7 junction of mGlu8, and anchors via hydrophobic interactions and water-mediated polar contacts, thereby stabilizing the active state of the receptor and exerting positive allosteric regulatory effects. VU6081679 can be used for research on Parkinson's disease.

AZ 12216052 is a mGluR8 positive allosteric modulator, and helps mGluR8 modulate signaling inputing to retinal ganglion cells. AZ 12216052 exhibits antianxiety effect.