LY3020371 hydrochloride exerts an antidepressant-like signature in vivo. LY3020371 hydrochloride is a potent, selective metabotropic glutamate 2/3 receptor (mGlu2/3) antagonist with Ki of 5.3 and 2.5 nM, potently blocks cAMP formation with IC50 of 16.2 nM.

mGluR3:2.5 nM (ki), mGluR2:5.3 nM (ki)

LY3020371 hydrochloride (LY3020371.HCl) (0.1 nM-100 μM; 1 hours) potently blocks mGlu2/3 agonist (DCG-IV)-inhibited, forskolin-stimulated cAMP formation (IC50=16.2 nM), an effect that was similarly observed in hmGlu3-expressing cells ( IC50=6.21 nM)[1]. LY3020371 hydrochloride (LY3020371.HCl) blocks agonist-suppressed spontaneous Ca2+ oscillations (IC50=34 nM) and in an intact hippocampal slice preparation (IC50=46 nM)[1].LY3020371 hydrochloride (LY3020371.HCl) displaces binding of the mGlu2/3 agonist ligand [3H]-459477 with high affinity (hmGlu2 Ki=5.26 nM;?hmGlu3 Ki=2.50 nM)[1].

LY3020371 hydrochloride (LY3020371) administered via intraperitoneal injection at doses of 3 mg/kg and 10 mg/kg, 2 hours prior, significantly promotes wakefulness, notably decreasing NREM sleep in Wistar rats during the light phase[3]. Intravenous administration of LY3020371 hydrochloride at a dosage range of 3-15 mg/kg in rats results in cerebrospinal fluid concentrations predicted to efficiently inhibit mGlu2/3 receptors[1].