XAP044 is a mGlu7-selective antagonist which inhibits lateral amygdala long term potentiation (LTP) in brain slices from wild type mice with a half-maximal blockade at 88 nm[1].

Previous study showed that in contrast to all previous mGlu7-selective drugs, XAP044 did not act through the seven-transmembrane region but rather via a binding pocket localized in mGlu7's extracellular Venus flytrap domain, a region identified for orthosteric agonist binding, which was suggested by the chimeric receptor studies in recombinant cell line assays [1].

In rodent behavioral paradigms, XAP044 demonstrated good brain exposure and wide spectrum anti-stress and antidepressant- and anxiolytic-like efficacy. In addition, XAP044 could reduce freezing during acquisition of Pavlovian fear and innate anxiety, which was consistent with the phenotypes of mGlu7-deficient mice. Moreover, XAP044 was able to inhibit lateral amygdala long term potentiation (LTP) in brain slices from wild type mice with a half-maximal blockade at 88 nm. It was alos found that there was no effect of XAP044 on LTP of mGlu7-deficient mice, suggesting that such pharmacological effect was mGlu7-dependent [1].