MMPIP is a reversible allosteric antagonist of the metabotropic glutamate receptor 7 (mGluR7) that blocks agonist-induced calcium mobilization (IC50 = 26 nM).1,2 It does not affect other mGlu receptors. The modulation of mGluR7 by MMPIP is context dependent, in that it is not observed in all known mGluR7 signaling pathways.2 MMPIP has been used to investigate the role of mGluR7 in cocaine-mediated reward signaling, attention and impulse control, and cognitive behavior in mice and rats.3,4,5 MMPIP also reversibly inhibits constitutive activity of mGluR7 in sympathetic neurons from the rat superior cervical ganglion.6
1.Suzuki, G., Tsukamoto, N., Fushiki, H., et al.In vitro pharmacological characterization of novel isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonistsJ. Pharmacol. Exp. Ther.323(1)147-156(2007) 2.Niswender, C.M., Johnson, K.A., Miller, N.R., et al.Context-dependent pharmacology exhibited by negative allosteric modulators of metabotropic glutamate receptor 7Mol. Pharmacol.77(3)459-468(2010) 3.Li, X., Li, J., Peng, X.Q., et al.Metabotropic glutamate receptor 7 modulates the rewarding effects of cocaine in rats: Involvement of a ventral pallidal GABAergic mechanismNeuropsychopharmacology34(7)1783-1796(2009) 4.Benn, A., and Robinson, E.S.J.Investigating glutamatergic mechanism in attention and impulse control using rats in a modified 5-choice serial reaction time taskPLoS One9(12)(2014) 5.Palazzo, E., Romano, R., Luongo, L., et al.MMPIP, an mGluR7-selective negative allosteric modulator, alleviates pain and normalizes affective and cognitive behavior in neuropathic micePain156(6)1060-1073(2015) 6.Kammemeier, P.J.Constitutive activity of metabotropic glutamate receptor 7BMC Neurosci.16:17(2015)