| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
Metabotropic glutamate receptor (mGluR)
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| ln Vitro |
Effects of LY341495 on Akt and Wnt pathway proteins [2]
The mGlu2/3 antagonist LY341495 was used to examine the effects of blocking the mGlu2/3 on Akt and Wnt pathway proteins. Repeated treatment with 3.0 mg/kg of LY341495 decreased Dvl-2, pGSK-3α/β and β-catenin protein levels but Dvl-1, Dvl-3 and GSK-3α/β were unaffected in both the PFC and STR (Fig. 3a and b). In addition, to changes in the Wnt proteins, a reduction in pAkt Ser473 but not in total Akt or pAkt Thr308 were observed in the PFC and STR (Fig. 3c and d). A lower dose of repeated LY341495 (1.0 mg/kg) was also used and had no effect on Akt or Wnt pathway proteins tested in the PFC or STR (data not shown). Finally, changes in Akt and Wnt pathway proteins were assessed following acute administration of LY341495. Decreases in pGSK-3α/β (Fig. 4a and b) and pAkt Ser473 (Fig. 4c and d) were observed in the PFC and STR following acute administration of LY341495 (3.0 mg/kg). Therefore, acute administration of LY341495 decreased pAkt and pGSK-3 levels but repeated treatment (3.0 mg/kg) is needed to reduce β-catenin levels. Furthermore, LY341495 had the generally the opposite effect following acute and chronic administration compared to mGlu2/3 agonist, LY379268. |
| ln Vivo |
LY341495 (0.3, 1 and 3 mg/kg, ip) exhibits lower levels of insight into the state [1]. LY341495 (3.0 mg/kg) reduced Dvl-2, pGSK-3α/β and β-catenin protein levels, but Dvl-1, Dvl-3 and GSK-3α/β were not activated in PFC and STR. Compared with the mGlu2/3 stimulant LY379268, LY341495 generally produces just the right effect after fast and fast[2]. c-Fos expression induced by LY341495 (3 mg/kg, i.p., 2.5 hours) was not altered in either KO brain. In mGluR3-KO, LY341495 has little activity in the central extended amygdala [central amygdala] nucleus, nucleus of cancellation (CeL) and bed nucleus of stria terminalis, dorsal nucleus (BSTLD) [3].
Experimental evidence suggests that metabotropic glutamate 2/3 (mGlu2/3) receptor antagonists affect cognitive function, although contradictory findings have been reported. To clarify the role of mGlu2/3 receptor antagonists in one aspect of cognition, the present study investigated the effects of a broad range of doses of the mGlu2/3 receptor antagonist LY341495 on post-training recognition memory components (storage and/or retrieval) in rats. The efficacy of LY341495 in antagonizing the extinction of recognition memory was also investigated. The novel object recognition test was used as the memory test. The highest LY341495 doses administered (0.3, 1, and 3 mg/kg) disrupted performance in this recognition memory procedure in rats at all delay conditions tested, whereas administration of lower doses (0.05 and 0.1 mg/kg) did not impair recognition memory. Moreover, administration of the low LY341495 doses (0.05 and 0.1 mg/kg) counteracted the extinction of recognition memory. The present results indicate that administration of the mGlu2/3 receptor antagonist LY341495 can either impair or enhance recognition memory in rats, depending on the dose of the compound and delay period used. Thus, together with previously reported findings, the present data suggest complex effects of this compound on cognitive function, particularly recognition memory.[1] |
| Animal Protocol |
Six experimental groups (each with ten rats) are created by randomly assigning the rats: vehicle and 0.05, 0.1, 0.3, 1, and 3 mg/kg LY341475. The LY341495 doses are selected on the basis of results from previous Published studies that evaluated the effects of this compound on cognition. Training: Two 2-minute trials were given to the rats during the training session. Right after T1, the animals are given either LY341495 or the vehicle. Given that untreated control rats in these experiments still have intact recognition memory, an ITI of one hour is employed with a 2-min trial duration.
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| References |
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| Additional Infomation |
The treatment of neuropathic pain remains a clinical challenge because of its unclear mechanisms and broad clinical morbidity. Matrix metalloproteinase (MMP)-9 and MMP-2 have previously been described as key components in neuropathic pain because of their facilitation of inflammatory cytokine maturation and induction of neural inflammation. Therefore, the inhibition of MMPs may represent a novel therapeutic approach to the treatment of neuropathic pain. In this study, we report that N-acetyl-cysteine (NAC), which is a broadly used respiratory drug, significantly attenuates neuropathic pain through a unique mechanism of MMP inhibition. Both the in vitro (0.1 mM) and in vivo application of NAC significantly suppressed the activity of MMP-9/2. Orally administered NAC (50, 100, and 200 mg/kg) not only postponed the occurrence but also inhibited the maintenance of chronic constrictive injury (CCI)-induced neuropathic pain in rats. The administration of NAC blocked the maturation of interleukin-1β, which is a critical substrate of MMPs, and markedly suppressed the neuronal activation induced by CCI, including inhibiting the phosphorylation of protein kinase Cγ, NMDAR1, and mitogen-activated protein kinases. Finally, NAC significantly inhibited CCI-induced microglia activation but elicited no notable effects on astrocytes. These results demonstrate an effective and safe approach that has been used clinically to alleviate neuropathic pain through the powerful inhibition of the activation of MMPs.[4]
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| Molecular Formula |
C20H19NO5
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| Molecular Weight |
353.37
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| Exact Mass |
353.126
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| Elemental Analysis |
C, 67.98; H, 5.42; N, 3.96; O, 22.64
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| Related CAS # |
LY341495;201943-63-7
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| PubChem CID |
10713043
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| Appearance |
White to off-white solid powder
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| LogP |
-0.2
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| InChi Key |
VLZBRVJVCCNPRJ-ZOSMMGSXSA-N
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| InChi Code |
InChI=1S/C20H19NO5/c21-20(19(24)25,15-9-13(15)18(22)23)10-14-11-5-1-3-7-16(11)26-17-8-4-2-6-12(14)17/h1-8,13-15H,9-10,21H2,(H,22,23)(H,24,25)/t13-,15-,20?/m0/s1
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| Chemical Name |
(1S,2S)-2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]cyclopropane-1-carboxylic acid
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| Synonyms |
(Rac)-LY341495; LY 341495; SCHEMBL24606222;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8299 mL | 14.1495 mL | 28.2990 mL | |
| 5 mM | 0.5660 mL | 2.8299 mL | 5.6598 mL | |
| 10 mM | 0.2830 mL | 1.4149 mL | 2.8299 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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