氨磺必利作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetAmisulprideCat. No.: HY-14545CAS No.: 71675-85-9分式: CHNOS分量: 369.48作靶點(diǎn): Dopamine 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 : 50 mg/mL (135.33 mM; Need ultrasonic)H2O : 0.2 mg/mL (0.54 mM; Need

2、 ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.7065 mL 13.5325 mL 27.0651 mL5 mM 0.5413 mL 2.7065 mL 5.4130 mL10 mM 0.2707 mL 1.3533 mL 2.7065 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

3、的實(shí)驗(yàn)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 (6.77 mM); Clear solution此案可獲得 2.5 mg/mL (6.77 mM，飽和度未

4、知) 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 (6.77 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (6.77 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 (6.77 mM); Clear solution; Need ultrasonic此案可獲得 2.5 mg/mL (6.77 mM) 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 Amisulpride種多

6、巴胺 D2/D3 受體拮抗劑，對(duì)于多巴胺 D2 和 D3 的 Ki 值分別為 2.8 和 3.2 nM。IC & Target Ki: 2.8 nM (D2 receptor), 3.2 nM (D3 receptor)1體外研究 Amisulpride is an atypical dopamine D2/D3 receptor antagonist with Kis of 2.8 and 3.2 nM for human dopamine D2and D3, respectively. Amisulpride (100 nM) inhibits quinpirole-elicited 3H

7、thymidine incorporation with an IC50 valueof 223 nM (n=3). Amisulpride slightly but significantly increases 3Hdopamine release from slices of the rat striatum(S2/S1=0.880.04 under control conditions, n=6; 1.040.08 in the presence of 100 nM Amisulpride,n=4; P0.05) andopposes the inhibitory effects of

8、 7-OH-DPAT in both brain areas1.體內(nèi)研究 Only the highest dose of Amisulpride (100 mg/kg) significantly reduces dopamine levels in the striatum or limbic system. Amisulpride significantly increases the synthesis of dopamine in the rat striatum and limbic system at doses of 20 and 100 mg/kg. Amisulpride

9、(0.5 to 75 mg/kg) fails to provoke an additional increase in dopa accumulation inthe striatum but slightly accelerates, at 75 mg/kg, dopamine synthesis in the limbic system. In comparison withvehicle-treated controls, Amisulpride (10 mg/kg) increases extracellular dopamine levels. The administration

10、 ofAmisulpride (0.5 to 15 mg/kg s.c.) provokes a time- and dose-dependent increase in the stimulation-evokeddopamine release. Amisulpride decreases striatal ACh levels significantly at 30 and 100 mg/kg (87.5% and 56.3% ofcontrol levels, respectively)1. In both acute study, Amisulpride (70 mg/kg, p.o

11、.) significantly increases the duration ofswimming behavior F(3,28)=45.90, p0.012.PROTOCOLCell Assay 1 The functional effects of Amisulpride at the dopamine D3 receptor subtype are assessed. Briefly, the mitogenicresponse elicited in NG108-15 neuroblastoma-glioma cells stably transfected with human

12、dopamine D3 receptorcDNA by the addition of 10 nM quinpirole in the presence of 1 M forskolin is quantified by the incorporation of 3Hthymidine. Antagonism of quinpirole-induced mitogenesis is measured in the presence of increasing (0.1 to 100nM) concentrations of Amisulpride1.MCE has not independen

13、tly confirmed the accuracy of these methods. They are for reference only.Animal A total of 64 male Swiss albino mice weighing between 20 to 30 g are used. The animals are fed with standard pelletAdministration 2 diet and water ad libitum. The mice are divided in different groups (n=8 in each group)

14、and drug administration isdone as follows: Group 1 (control): distilled water (1 mL/kg) 23.5, 5 and 1 h before the test. Group 3 (Amisulpride):Amisulpride (70 mg/kg) 23.5, 5 and 1 h before the test2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERE

15、NCESPage 2 of 3 www.MedChemE1. Schoemaker H, et al. Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor antagonist with both presynaptic and limbicselectivity. J Pharmacol Exp Ther. 1997 Jan;280(1):83-97.2. Pawar GR, et al. Evaluation of antidepressant like property of amisulpride per se and its comparison with fluoxetine and olanzapine using forcedswimming test in albino mice. Acta Pol Pharm. 2009 May-Jun;66