mGluR2R ( IC50 = 5 nM ); mGluR3R ( IC50 = 24 nM )

LY-354740 (15 or 30 mg/kg, i.p.) has no effect on spatial working memory performance. It also has no effect in rewarded alternation testing with a short inter-trial interval when used at a dose of 30 mg/kg in both Gria1−/− and WT mice. LY354740 (15 or 30 mg/kg, i.p.) decreases spontaneous locomotor activity in wild-type and Gria1−/− mice. In male naive GluA1-KO and pre-handled GluA1-KO animals, LY354740 (15 mg/kg, i.p.) reduces novelty-induced hyperlocomotion, but not in females. The increased c-Fos expression in GluA1-KO males is significantly reduced to WT male levels by LY354740 (15 mg/kg, i.p.), but not in females[3]. The immobilization stress-induced rise in BDNF mRNA expression in the rat mPFC is attenuated by LY354740 (10 mg/kg, i.p.)[4]. In the rat mPFC, LY354740 (10 mg/kg, i.p.) reduces the rise in BDNF mRNA expression brought on by immobilization stress[4].

Mice: Experiment 1A involves 30 drug-free testing trials (five trials per day for six days) for wild-type (female: N = 6; male: N = 5) and Gria1^−/− (female: N = 7; male: N = 8) mice. Each animal is then tested on rewarded alternation following an injection of either Eglumegad (LY354740) (15 mg/kg) or vehicle. Animals are given injections, and then they are kept in their home cage for 30 minutes before behavioral testing starts. In the T-maze, ten trials of rewarded alternation are given to each animal. Mice are allowed a maximum of 120 seconds to finish a trial. The animals are retested without receiving any medication at least 24 hours after the initial round of drug testing to make sure the drug has no long-term effects and the mice continue to perform at a high level during alternation. After retesting for twenty-four hours, mice are given ten more trials of rewarded alternation testing, but this time they are administered a drug that they have not previously received. Considering the quantity of mice, every effort is made to counterbalance the order of drug exposure within genotype and sex. All trials in which the animal alternated are counted, along with the amount of time it took to run (sample latency) from the start arm to the food well and the amount of time it took to make a decision (choice latency) during the choice run. Utilizing a stopwatch, the researcher determines latencies. For the duration of the experiment, the researcher is blind to the animals' genotype and drug allocations. A higher dose of Eglumegad (LY354740) (30 mg/kg) or a vehicle is given to distinct groups of male wild-type (N = 7) and Gria1^−/− mice (N = 7) after they undergo the same procedure as in Experiment 1A. The process used in Experiment 1B is then repeated in Experiment 1C to examine the possible effects of increased proactive interference. The drug dose (30 mg/kg) and the mice are used, but a modified testing protocol is used this time, reducing the interval between trials to 20 s. Rats: Two experiments are conducted. In the first experiment, rats kept in their home cages or rats exposed to two hours of immobilization stress in plastic cones are compared for the effects of LY354740 (10 mg/kg, i.p., neutralized to a pH ~ 7.4) or vehicle (0.9% saline neutralized to pH ~ 7.4) (n = 7, cage control/vehicle; n = 7, cage control/LY354740; n = 6, stress/vehicle; n = 6, stress/Eglumegad (LY354740)). In the second experiment, rats given a 2-hour immobilization stress are compared to rats given vehicle in their home cages, or two lower doses of LY354740 (1 and 3 mg/kg, i.p.) or vehicle (n = 4 for all groups). Fifteen minutes before they are placed in plastic cones with the open end tightly closed, all animals receive an injection of either Eglumegad (LY354740) or a vehicle. Every immobilized rat is taken to a quiet room away from the animal colony, put in a plexiglass chamber with bedding on the bottom, and then put right into a plastic cone. The rats are beheaded and placed in the plastic containers; this is done two hours later. After removal, the brains are preserved at -80°C by freezing them on dry ice.

[1]. The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice. Eur J Neurosci. 2017 Apr;45(7):912-921.

[2]. Levels of the Rab GDP dissociation inhibitor (GDI) are altered in the prenatal restrain stress mouse model of schizophrenia and are differentially regulated by the mGlu2/3 receptor agonists, LY379268 and LY354740. Neuropharmacology. 2014 Nov:86:133-44.

[3]. Reversal of novelty-induced hyperlocomotion and hippocampal c-Fos expression in GluA1 knockout male mice by the mGluR2/3 agonist LY354740. Neuroscience. 2013 Oct 10:250:189-200.

[4]. The mGlu2/3 receptor agonist LY354740 suppresses immobilization stress-induced increase in rat prefrontal cortical BDNF mRNA expression. Neurosci Lett. 2006 May 8;398(3):328-32.

C8H11NO4

185.17724

185.07

C, 51.89; H, 5.99; N, 7.56; O, 34.56

176199-48-7

(rel)-Eglumegad; 176027-90-0; Eglumegad hydrochloride

Solid powder

C1C[C@]([C@H]2[C@@H]1[C@@H]2C(=O)O)(C(=O)O)N

VTAARTQTOOYTES-RGDLXGNYSA-N

InChI=1S/C8H11NO4/c9-8(7(12)13)2-1-3-4(5(3)8)6(10)11/h3-5H,1-2,9H2,(H,10,11)(H,12,13)/t3-,4-,5-,8-/m0/s1

(1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid

LY354740; LY-354740; LY 354740

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~33.3 mg/mL (~180 mM)
H2O: ~6.3 mg/mL (~34.2 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (13.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 2: 2.86 mg/mL (15.44 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)