VU036172 is a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5; Ki = 195 nM).1 It is selective for mGluR5 over mGluR1, mGluR3, and mGluR4 at 10 ?M. VU036172 (20 and 50 ?M) prevents TNF-α and nitric oxide (NO) production by IFN-γ- or LPS-stimulated BV-2 and primary microglial cells.2 It reduces the expression of inducible nitric oxide synthase (iNOS) and increases the expression of Ym1 and arginase 1 in LPS-stimulated BV-2 cells when used at a concentration of 20 ?M. VU036172 (50 mg/kg) reduces the size of cortical lesions, prevents neuronal degeneration, and improves sensorimotor deficits in the beam walk test in a mouse model of traumatic brain injury (TBI), indicating improved recovery of motor function.
1.Rodriguez, A.L., Grier, M.D., Jones, C.K., et al.Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activityMol. Pharmacol.78(6)1105-1123(2010) 2.Loane, D.J., Stoica, B.A., Tchantchou, F., et al.Novel mGluR5 positive allosteric modulator improves functional recovery, attenuates neurodegeneration, and alters microglial polarization after experimental traumatic brain injuryNeurotherapeutics11(4)857-869(2014)