鹽酸帕羅西汀作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetParoxetine hydrochlorideCat. No.: HY-B0492CAS No.: 78246-49-8分式: CHClFNO分量: 365.83作靶點: Serotonin Transporter; Autophagy作通路: Neuronal Signaling; Autophagy儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (273.35 mM; Need ultrasonic)H2O

2、: 5 mg/mL (13.67 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 2.7335 mL 13.6676 mL 27.3351 mL5 mM 0.5467 mL 2.7335 mL 5.4670 mL10 mM 0.2734 mL 1.3668 mL 2.7335 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-

3、20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，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；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.83 mM); Clear solution此案可獲

4、得 2.5 mg/mL (6.83 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 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. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.83 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (6.83 mM，飽和度未知) 的

5、澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.83 mM); Clear solution此案可獲得 2.5 mg/mL (6.83 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性

6、 Paroxetine hydrochloride種抗抑郁藥，為效的五羥胺再攝取抑制劑，能抑制 GRK2 活性，IC50 值為 14 M。IC & Target IC50: 14 M (GRK2)3體外研究 Paroxetine (1 M and 10 M) distinctly restrains T cell migration induced by CX3CL1 through inhibiting GRK2.Paroxetine inhibits GRK2 induced activation of ERK1. Paroxetine (10 M) reduces pro-inflamm

7、atory cytokines in LPS-stimulated BV2 cells. Paroxetine (0-5 M) leads to a dose-dependent inhibition on LPS-induced production of TNF-and IL-1 in BV2 cells. Paroxetine also inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production andinducible nitric oxide synthase (iNOS) expression in

8、BV2 cells. Paroxetine (5 M) blocks LPS-induced JNK activationand attenuates baseline ERK1/2 activity in BV2 cells. Paroxetine relieves microglia-mediated neurotoxicity, andsuppresses LPS-stimulated pro-inflammatory cytokines and NO in primary microglial cells4.體內(nèi)研究 Paroxetine treatment obviously att

9、enuates the symptoms of CIA rats. Paroxetine treatment clearly prevents thehistological damage of joints and alleviates T cells infiltration into synovial tissue. Paroxetine reveals a strong effect oninhibiting CX3CL1 production in synovial tissues1. Paroxetine (20 mg/kg/day) reduces the myocyte cro

10、ss-sectionalarea in rat and ROS formation in the remote myocardium. Paroxetine reduces the susceptibility to ventriculartachycardia. Paroxetine treatment following MI decreases LV remodeling and susceptibility to arrhythmias, probablyby reducing ROS formation2. In CCI paroxetine-treated group, parox

11、etine (10 mg/kg, i.p.) produces hyperalgesia atdays 7 and 10 (P0.01), but a decrease in pain behavior is seen at day 14. Moreover, paroxetine (10 mg/kg)significantly attenuates tactile hypersensitivity when compared to CCI vehicle-treated group5.PROTOCOLCell Assay 4 Cell viability is determined by t

12、he tetrazolium salt 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide(MTT) assay. BV2 and primary microglial cells are initially seeded into 96-well plates at a density of 1104 cells/welland 5104 cells/well, respectively. Following treatment, MTT (5 mg/mL in PBS) is added to each well and i

13、ncubated at37C for four hours. The resulting formazan crystals are dissolved in dimethylsulfoxide (DMSO). The optical density ismeasured at 570 nm, and results are expressed as a percentage of surviving cells compared with the control.MCE has not independently confirmed the accuracy of these methods

14、. They are for reference only.Animal Animals are divided into two main groups: 1) pre-emptive and 2) post-injury group. Each main group is divided intoAdministration 5 three different subgroups: I) CCI vehicle-treated group, II) sham group, and III) CCI paroxetine-treated group. Vehicleis injected i

15、.p. to CCI and sham-operated animals. In the pre-emptive study, paroxetine (10 mg/kg) is injected 1 hbefore surgery and continued daily until day 14 post surgery. In the post-injury group, paroxetine (10 mg/kg) isadministered at day 7 post injury and continued daily until day 14. All behavioral test

16、s are recorded on day 0 (controlday) before surgery and on days 1, 3, 5, 7, 10, and 14 post-nerve injury.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Brain Res. 2019 Jun 15. pii: S0006-8993(19)30342-7.See more cust

17、omer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Wang Q, et al. Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis. Sci Rep. 2017 Mar 28;7:45364.2. Lassen TR, et al. Effect of paroxetine on left ventricular remodeling in an in vi

18、vo rat model of myocardial infarction. Basic Res Cardiol. 2017 May;112(3):26.3. Waldschmidt HV, et al. Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine. JMed Chem. 2017 Apr 13;60(7):3052-3069.4. Liu RP, et al. Paroxetine ameliorates lipopolysaccharide-induced microglia activation via differential regulation of MAPK signaling. J Neuroinflammation.2014 Mar 12;11:47.5. Zarei M, et al. Paroxetine attenuates the development and existing pain in a ra