Administered orally, ADX88178 demonstrates a dose-responsive enhancement in exploratory behavior in mice, evident by increased open-arm entries in the elevated plus maze (EPM) test. Specifically, doses of 3, 10, and 30 mg/kg of ADX88178 result in 5-, 7-, and nearly 13-fold surges in open-arm entries, respectively, in comparison to those given the vehicle control. Similarly, the time mice spend in the open arms escalates dose-dependently; at doses of 3, 10, and 30 mg/kg, there are increases of 8-, 12-, and 24-fold, respectively, relative to the vehicle controls. In rats, oral doses of ADX88178 ranging from 10 to 100 mg/kg also show a dose-dependent elevation in the EPM test's open-arm entries. At concentrations of 10, 30, and 100 mg/kg, the increases are 5-, 8-, and more than 10-fold, respectively, compared with vehicle-treated counterparts. Additionally, the duration spent in the open arms by rats rises in a dose-dependent manner; with 10, 30, and 100 mg/kg doses leading to 7.5-, 11-, and 13-fold increases, respectively, when juxtaposed with the controls. This behavior indicates a significant anxiolytic effect of ADX88178 in rodent models, improving their exploratory behavior and reducing anxiety-like symptoms as the dosage increases^[3].

ADX88178 is a highly potent and selective positive allosteric modulator of the metabotropic glutamate receptor subtype 4 (mGluR4), serving as a novel radioligand for mGluR4 imaging. It enhances glutamate-induced activation of human mGluR4 with EC50 values as low as 4 nM, showing negligible effects on other mGluR subtypes (EC50 > 30 μM), which underlines its specificity^[1].

Furthermore, ADX88178 demonstrates brain penetrance and selectivity as a positive allosteric modulator of mGluR4. In studies involving microglia pre-treated with ADX88178 or LAP4 before exposure to LPS, both treatments significantly reduce TNFα levels, indicating their anti-inflammatory potential. Remarkably, even a minimal concentration of 1 nM ADX88178 is effective in suppressing TNFα production, maintaining its efficacy at higher concentrations of 10 and 100 nM. This suggests ADX88178's potent anti-inflammatory action at remarkably low doses^[2].