AMN082 free base

AMN082 is an orally bioavailable allosteric agonist of metabotropic glutamate receptor 7 (mGluR7).¹ It inhibits cAMP accumulation induced by forskolin in CHO cells expressing human mGluR7b (EC₅₀ = 64 nM). AMN082 (10 μM) is selective for mGluR7a and mGluR7b over mGluR1b, mGluR4, and mGluR8a with 140, 90, 15, 18, and 20% activation, respectively, as well as over mGluR2, mGluR3, mGluR5a, mGluR6, GluR3, and NMDA receptors containing NR1a, NR2A, or NR2B subunits. AMN082 also binds to the norepinephrine transporter (NET) and α₁-adrenergic receptor (α₁-AR).² It increases the proliferation of neural progenitor cells (NPCs) and induces their differentiation into neurons when used at a concentration of 1 μM.³ AMN082 (2.5 mg/kg) inhibits apomorphine-induced circling in a rat model of Parkinson's disease induced by 6-hydroxy dopamine .⁴

1.Mitsukawa, K., Yamamoto, R., Ofner, S., et al.A selective metabotropic glutamate receptor 7 agonist: Activation of receptor signaling via an allosteric site modulates stress parameters in vivoProc. Natl. Acad. Sci. USA102(51)18712-18717(2005) 2.Sukoff Rizzo, S.J., Leonard, S.K., Gilbert, A., et al.The metabotropic glutamate receptor 7 allosteric modulator AMN082: A monoaminergic agent in disguise?J. Pharmacol. Exp. Ther.338(1)345-352(2011) 3.Tian, Y., Liu, Y., Chen, X., et al.AMN082 promotes the proliferation and differentiation of neural progenitor cells with influence on phosphorylation of MAPK signaling pathwaysNeurochem. Int.57(1)8-15(2010) 4.Greco, B., Lopez, S., van der Putten, H., et al.Metabotropic glutamate 7 receptor subtype modulates motor symptoms in rodent models of Parkinson's diseaseJ. Pharmacol. Exp. Ther.332(3)1064-1071(2010)