mGluR5 modulator 1 is a compound that acts as a positive allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGluR5). Its primary application lies in the field of schizophrenia and cognitive impairment research.

mGluR5 modulator 1, identified as compound 2c at concentrations ranging from 0.1 to 0.00001 nM, enhances L-glutamate and DHPG-induced responses to levels comparable with those of orthosteric agonists in calcium (Ca 2+) mobilization and inositol monophosphate (IP1) accumulation assays. Furthermore, at the same concentrations, it surpasses the maximal response of orthosteric agonists in ERK1/2 phosphorylation assays, indicating an enhanced activation. Additionally, mGluR5 modulator 1 triggers mGlu5 receptor internalization independently of the presence of orthosteric agonists or antagonists. It also amplifies the effects of orthosteric agonists (L-glutamate or DHPG) in Ca 2+ mobilization, IP1 accumulation, and ERK1/2 phosphorylation in HEK293A-mGlu5-low cells, demonstrating significant potency and effectiveness (pK B values of 5.4 and 5.3 for Ca 2+ mobilization, 5.88 and 5.4 for ERK1/2 phosphorylation, respectively). In cortical neurons, mGluR5 modulator 1 further strengthens DHPG's impact, evidenced by pEC50 values of 6.32 and 6.33 in Ca 2+ mobilization and IP1 accumulation, showcasing its potential in modulating glutamatergic responses [1].