Description
AMN082 is an orally bioavailable allosteric agonist of metabotropic glutamate receptor 7 (mGluR7). It inhibits cAMP accumulation induced by forskolin in CHO cells expressing human mGluR7b (EC
50 = 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 α
1-adrenergic receptor (α
1-AR). It increases the proliferation of neural progenitor cells (NPCs) and induces their differentiation into neurons when used at a concentration of 1 μM. AMN082 (2.5 mg/kg) inhibits apomorphine-induced circling in a rat model of Parkinson''s disease induced by 6-hydroxy dopamine (6-OHDA; ).
Uses
AMN082 dihydrochloride is a selective agonist at mGluR-7.
Definition
ChEBI: AMN082 dihydrochloride is a hydrochloride obtained by combining N,N'-bis(diphenylmethyl)ethane-1,2-diamine with two molar equivalent of hydrochloric acid. It has a role as a metabotropic glutamate receptor agonist, a geroprotector and a neuroprotective agent. It contains a N,N'-bis(diphenylmethyl)ethane-1,2-diamine(2+).
in vivo
treatment with amn082 was shown to penetrate into the brain and hence it modulated the level of stress hormones (acth and cortisol) in wild type animal. but these effects were not found in the mglur7 ko mouse [2].
References
[1]. pelkey ka, yuan x, lavezzari g, et al. mglur7 undergoes rapid internalization in response to activation by the allosteric agonist amn082. neuropharmacology, 2007, 52(1): 108-117.
[2]. gasparini f, spooren w. allosteric modulators for mglu receptors. current neuropharmacology, 2007, 5(3): 187-194.
