阿戈美拉汀作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetAgomelatineCat. No.: HY-17038CAS No.: 138112-76-2分式: CHNO分量: 243.3作靶點(diǎn): Melatonin Receptor; 5-HT Receptor作通路: GPCR/G Protein; Neuronal Signaling儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (411.02 mM)* means soluble, but saturation

2、 unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 4.1102 mL 20.5508 mL 41.1015 mL5 mM 0.8220 mL 4.1102 mL 8.2203 mL10 mM 0.4110 mL 2.0551 mL 4.1102 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)

3、動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (10.28 mM); Clear solution此案可獲得 2.5 mg/mL (10.28 mM，飽和度未知

4、) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (10.28 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (10.28 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L

5、 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (10.28 mM); Clear solution此案可獲得 2.5 mg/mL (10.28 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Agomelatine (S-20098)

6、種 MT1 和 MT2 受體的特異性激動(dòng)劑，對(duì) CHO-hMT1，HEK-hMT1，CHO-hMT2，HEK-hMT2 的 Ki 分別為 0.1，0.06，0.12 和 0.27 nM1。Agomelatine 還和克隆的 5-HT2C 受體中 pKi 分別為 6.4 和 6.22。種選擇性的 5-HT2C 受體拮抗劑，在天然 (豬)IC & Target 5-HT2C Receptor 5-HT2C Receptor hMT1 hMT16.4 (pKi, native porcine) 6.2 (pKi, human) 0.1 nM (Ki, CHO Cells) 0.06 nM (Ki,

7、HEK Cells)hMT2 hMT20.12 nM (Ki, CHO Cells) 0.27 nM (Ki, HEK Cells)體外研究 Agomelatine (S 20098) acts as a full agonist of MT1 and MT2 receptors with EC50s of 1.60.4, 0.100.04 nM for CHOhMT1, CHO-hMT2 (h1 and h2 receptors expressed in CHO or HEK cell membranes)1.Agomelatine (S20098) also interacts with

8、h5-HT2B receptors (6.6), whereas Agomelatine shows low affinity at native(rat)/cloned, human 5-HT2A (5.0/5.3) and 5-HT1A (5.0/5.2) receptors, and negligible (5.0) affinity for other 5-HTreceptors2.體內(nèi)研究 Agomelatine (25, 50, or 75 mg/kg; i.p.) has antioxidant activity in Strychnine (75 mg/kg, i.p.) or

9、 Pilocarpine (400mg/kg, i.p.) induced seizure models in mice. Agomelatine dose not have any antioxidant effects on parameters ofoxidative stress produced by Pentylenetetrazole (PTZ) or Picrotoxin (PTX) induced seizure models when compared tocontrols3.Animal Model: Female Swiss mice (20-30 g) were ad

10、ministered PTZ (85 mg/kg, i.p.), PTX (7 mg/kg,i.p.), strychnine (75 mg/kg, i.p.), Pilocarpine (400 mg/kg, i.p.), respectively3.Dosage: 25, 50, or 75 mg/kgAdministration: Administered intraperitoneally (i.p.)Result: All dosages showed a significant decrease in thiobarbituric acid reactive substances(

11、TBARS) levels and nitrite content in all brain areas when compared to controls in thePilocarpine induced seizure model.All dosages decreased TBARS levels in all brain areas, and at low doses (25 or 50mg/kg) decreased nitrite contents, but only at 25 or 50 mg/kg showed a significantincrease in catala

12、se activity in three brain areas when compared to controls in theStrychnine-induced seizure model.Did not have any antioxidant effects on parameters of oxidative stress produced byPTX- or PTZ-induced seizure models when compared to controls.Page 2 of 3 www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Protein Cell. 2019 Mar;

13、10(3):178-195.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Audinot V, et al. New selective ligands of human cloned melatonin MT1 and MT2 receptors. Naunyn Schmiedebergs Arch Pharmacol. 2003Jun;367(6):553-61.2. Millan MJ, et al. The novel melatonin agonist agomelat

14、ine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhancesthe activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther. 2003 Sep;306(3):954-64.3. Aguiar CC, et al. Effects of agomelatine on oxidative stress in the brain of mice after chemically induced seizures. Cell Mol Neurobiol. 2013Aug;33(6):825-35.McePdfHe