Basimglurant (RG7090) is a potent, selective, and safe mGlu5 inhibitor with good oral bioavailability and long half-life supportive of once-daily administration, good brain penetration, and high in vivo potency. Its ability to alleviate symptoms of depression is validated through functional magnetic resonance imaging (fMRI) assessments, alongside its capacity to produce anxiolytic-like and antinociceptive effects^[1].

Basimglurant is undergoing phase II clinical trials for depression and fragile X syndrome treatment, Basimglurant consistently extends drinking time in the Vogel conflict drinking test in a dose-dependent manner. Effective doses of Basimglurant (RG7090) yield a plasma exposure range from 5 ng/mL (0.03 mg/kg) to 37 ng/mL (0.3 mg/kg)^[2].

Detailed analysis using [³H]-basimglurant on recombinant human mGlu5 receptors shows monophasic saturation isotherms with a Kd of 1.1 nM. In competitive binding assays, Basimglurant effectively displaces [³H]-MPEP and [³H]-ABP688 with Ki values of 35.6 nM and 1.4 nM, respectively. Moreover, in HEK293 cells expressing human mGlu5, it inhibits quisqualate-induced Ca2+ mobilization and [³H]-inositolphosphate accumulation with IC50 values of 7.0 nM and 5.9 nM, respectively. Its efficacies are consistent across both human and rodent mGlu5 receptor orthologues.