阿戈美拉汀作用机制 - Medchemexpress - MCE中国

1、Product Data SheetAgomelatineCat. No.: HY-17038CAS No.: 138112-76-2分式: CHNO分量: 243.3作靶点: Melatonin Receptor; 5-HT Receptor作通路: GPCR/G Protein; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (411.02 mM)* means soluble, but saturation

2、 unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验

3、动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (10.28 mM); Clear solution此案可获得 2.5 mg/mL (10.28 mM，饱和度未知

4、) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (10.28 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (10.28 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L

5、 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (10.28 mM); Clear solution此案可获得 2.5 mg/mL (10.28 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Agomelatine (S-20098)

6、种 MT1 和 MT2 受体的特异性激动剂，对 CHO-hMT1，HEK-hMT1，CHO-hMT2，HEK-hMT2 的 Ki 分别为 0.1，0.06，0.12 和 0.27 nM1。Agomelatine 还和克隆的 5-HT2C 受体中 pKi 分别为 6.4 和 6.22。种选择性的 5-HT2C 受体拮抗剂，在天然 (猪)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)体外研究 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.体内研究 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户使本产品发表的科研献 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