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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 (6-OHDA; Item No. 25330).4
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1. A selective metabotropic glutamate receptor 7 agonist: Activation of receptor signaling via an allosteric site modulates stress parameters in vivo. Proc. Natl. Acad. Sci. USA 102(51), 18712-18717 (2005).
2. The metabotropic glutamate receptor 7 allosteric modulator AMN082: A monoaminergic agent in disguise? J. Pharmacol. Exp. Ther. 338(1), 345-352 (2011).
3. AMN082 promotes the proliferation and differentiation of neural progenitor cells with influence on phosphorylation of MAPK signaling pathways. Neurochem. Int. 57(1), 8-15 (2010).
4. Metabotropic glutamate 7 receptor subtype modulates motor symptoms in rodent models of Parkinson’s disease. J. Pharmacol. Exp. Ther. 332(3), 1064-1071 (2010).