| Description | 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. |
| In vitro | 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]. |
| In vivo | LY3020371 hydrochloride (LY3020371) (intraperitoneal injection; 3 mg/kg, 10?mg/kg; 2 hours) has clear wake promoting effects, resulting in a large reduction in NREM sleep in the Wistar rats during the light phase[3].LY3020371 hydrochloride (Intravenous injection; 3-15 mg/kg) in rats leads to cerebrospinal fluid drug levels that are expected to effectively block mGlu2/3receptors[1]. |
| Target activity | mGluR3:2.5 nM (ki), mGluR2:5.3 nM (ki) |
| molecular weight | 395.81 |
| Molecular formula | C15H16ClF2NO5S |
| CAS | 1377615-44-5 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| References | 1. Witkin JM, et al. In vitro pharmacological and rat pharmacokinetic characterization of LY3020371, a potent and selective mGlu2/3 receptor antagonist. Neuropharmacology. 2017 Mar 15;115:100-114. 2. Witkin JM, et al. Preclinical predictors that the orthosteric mGlu2/3 receptor antagonist LY3020371 will not engender ketamine-associated neurotoxic, motor, cognitive, subjective, or abuse-liability-related effects. Pharmacol Biochem Behav. 2017 Apr;155:43-55. 3. Wood CM, et al. Investigating the role of mGluR2 versus mGluR3 in antipsychotic-like effects, sleep-wake architecture and network oscillatory activity using novel Han Wistar rats lacking mGluR2 expression. Neuropharmacology. 2018 Sep 15;140:246-259. |