LY3020371 is a highly potent and selective antagonist targeting the glutamate (mGlu) 2/3 receptor, showcasing excellent inhibition at Ki values of 5.26 nM and 2.50 nM for hmGluR2 and hmGluR3, respectively. With its remarkable affinity and specificity, LY3020371 serves as a valuable tool in depression research.

mGluR2 (human):5.26 nM (Ki), mGluR3 (human):2.50 nM (Ki)

LY3020371 (0.1 nM-100 μM) competitively displaces binding of the mGlu2/3 agonist ligand [ 3 H]-459477 with high affinity[1]. LY3020371 (0.1 nM-100 μM) blocks DCG-IV-induced inhibition of forskolin-stimulated cAMP production in cells expressing recombinant human mGlu2 (IC 50 =16.2 nM) and mGlu3 (IC 50 =6.21 nM) receptors[1]. LY3020371 (0.3-30000 nM) exhibits concentration-dependent antagonism of LY379268-inhibited cAMP formation[1]. LY3020371 (1-10000 nM) reverses LY379268-suppressed, K + -evoked glutamate release, with an IC 50 of 86 nM[1]. LY3020371 (0.3-10000 nM) leads to a concentration-dependent and complete blockade of the LY379268-suppressed response, with an IC 50 of 33.9 nM[1].

LY3020371 (0.3-3 mg/kg, a single i.v.) significantly increases the number of spontaneously active dopamine cells in the ventral tegmental area (VTA) of rats[2]. LY3020371 (1-10 mg/kg, i.p. once a week for 5 weeks) dose dependently increases tissue oxygen in the anterior cingulate cortex (ACC) of rats[2]. LY3020371 (10 mg/kg, a single i.p.) increases in monoamine efflux in the medial prefrontal cortex of freely moving rats[2]. LY3020371 (1-30 mg/kg, a single i.v.) increases the cumulative wake time of rats in a dose- and time-dependent manner without rebound hypersomnolence[2]. LY3020371 (0.1-10 mg/kg, a single i.v.) decrease the time rats are immobile in the forced-swim test in the rat forced-swim assay[2]. Animal Model: Male Sprague-Dawley rats (230-350 g)[1]Dosage: 0.3, 1, 3 mg/kg Administration: I.v. daily 5 days per week for 2 weeks Result: Increased the number of actively firing dopamine neurons in the VTA of anesthetized rats.