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ML-396 is a positive allosteric modulator of group III metabotropic glutamate receptors (mGluRs) with EC50 values of 108, 146, and 128 nM for mGluR4, mGluR7, and mGluR8, respectively, in calcium mobilization assays.1 ML-396 potentiates LSP4-2022-induced reductions in paired-pulse field excitatory post synaptic potential (fEPSP) slopes in mouse hippocampal slices. In vivo, ML-396 (30 mg/kg) restores hippocampal long-term potentiation, improves novel object recognition, contextual fear learning, and social memory, and decreases sleep apneas in the Mecp2-/- mouse model of Rett syndrome.2
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1. Identification of positive allosteric modulators VU0155094 (ML397) and VU0422288 (ML396) reveals new insights into the biology of metabotropic glutamate receptor 7. ACS Chem. Neurosci. 5(12), 1221-1237 (2014).
2. mGlu7 potentiation rescues cognitive, social, and respiratory phenotypes in a mouse model of Rett syndrome. Sci. Transl. Med. 9(403), (2017).