AMN082 (free base)

AMN082 free base, a selective, orally active, and brain penetrant mGluR7 agonist, directly activates receptor signaling via an allosteric site in the transmembrane domain. AMN082 free base potently inhibits cAMP accumulation and stimulates GTPγS binding (EC₅₀ values, 64-290 nM) at transfected mammalian cells expressing mGluR7. AMN082 free base shows selectivity over other mGluR subtypes and selected ionotropic glutamate receptors. Antidepressant effects^[1][2]. IC50 & Target:mGluR7^[1] In Vitro: Preincubation of the synaptosomes with AMN082 (1 μM) for 10 min before 4-aminopyridine treatment efficiently inhibits the 4-aminopyridine-evoked release of glutamate, without altering the basal release of glutamate^[2]. In Vivo: AMN082 (6 mg/kg; p.o.) induces stress hormone increases in an mGluR7-dependent fashion in mGluR7^+/+ mice (C57BL/6 genetic background)^[1].
AMN082 (1.25-5.0 mg/kg, i.p.; 30 min before every Cocaine injection during repeated drug administration or before Cocaine challenge) dose-dependently attenuates the development, as well as the expression of Cocaine locomotor sensitization^[3].