羅替戈汀鹽酸鹽作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetRotigotine HydrochlorideCat. No.: HY-A0007CAS No.: 125572-93-2分式: CHClNOS分量: 351.93作靶點(diǎn): Dopamine Receptor; Adrenergic 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 : 50 mg/mL (142.0

2、7 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.8415 mL 14.2074 mL 28.4147 mL5 mM 0.5683 mL 2.8415 mL 5.6829 mL10 mM 0.2841 mL 1.4207 mL 2.8415 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)?/p>

3、 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)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 (7.10 mM); Clear solu

4、tion此案可獲得 2.5 mg/mL (7.10 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(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 (7.10 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (7.10 mM，

5、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(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 (7.10 mM); Clear solution此案可獲得 2.5 mg/mL (7.10 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 ACT

6、IVITY物活性 Rotigotine Hydrochloride (N-0923 Hydrochloride)是dopamine receptor 純激動(dòng)劑，是5-HT1A receptor 的部分激動(dòng)劑，以及 2B-adrenergic receptor 的拮抗劑，Ki 值分別為 0.71 nM (dopamine D3 receptor)，4-15 nM (D2，D5，D4receptors)，83 nM (dopamine D1 receptor)。IC & Target Ki: 0.71 nM (dopamine D3 receptor), 4-15 nM (dopamine D2,

7、 D5, D4 receptors), 83 nM (dopamine D1 receptor)12,176 nM (1A), 273 nM (1B), 338 nM (2A), 27 nM (2B), 30 nM (5-HT1A), 86 nM (5-HT7)2體外研究 Rotigotine (N-0923) has a 10-fold selectivity for D3 (pKi 9.2) receptors compared with D2, D4 and D5 (pKi 8.5-8.0) anda 100-fold selectivity compared with D1 recep

8、tors (pKi 7.2). In functional studies, Rotigotine (N-0923) behaves as fullagonist at all dopamine receptors but notably the potency for stimulation of D1 receptors is similar to that for D2 andD3 receptors (pEC50 respectively: 9.0, 9.4-8.6, 9.7)1. Rotigotine (N-0923) (10 M) decreases the number of T

9、Hirneurons by 40% in primary mesencephalic cell culture. Rotigotine (0.01 M) slightly protects dopaminergic neuronsagainst MPP+ toxicity, significantly protects dopaminergic neurons against rotenone-induced cell death, andsignificantly inhibits ROS production by rotenone4.體內(nèi)研究 In primed rats, Rotigo

10、tine (N-0923) (0.035, 0.1 and 0.35 mg/kg) induces contralateral turning behavior in a dosedependent manner. In drug naive rats, the turning behavior induced by Rotigotine, either alone or in combination with SCH 39166, is reduced compared to primed rats3.PROTOCOLKinase Assay 1 Binding assays are per

11、formed in 96-well polypropylene tubes in a final volume of 2 mL for D1 and D4 membranesand 1 mL for D2, D3 and D5 membranes containing: 50 L radioligand, 10 L drug/buffer/non-specific binding, buffer(final concentration 50 mM Tris-HCl pH 7.4, MgCl2 2 mM) and membranes (5 g protein for D2 and D3 and

12、25 gprotein for D1 and D5). Following 120 min of incubation at 25C, bound radioligand is determined by rapid vacuumfiltration through A/C glass fibre filters presoaked in 0.1% polyethylenimine. The filters are washed four times with 2mL ice-cold ishing buffer (Tris-HCl 50 mM, pH 7.4 at 4C) and retai

13、ned radioactivity is determined by liquidscintillation counting.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Primed rats: Two weeks after the 6-OHDA lesions, rats are primed with apomorphine (0.5 mg/kg s.c.). Rats showingAdministration 3 less

14、than 150 contralateral rotations during the 1 h testing period are excluded from the study. Three days afterpriming, rats are divided into different experimental groups and treated with different doses of the dopaminereceptor agonists (Rotigotine or pramipexole) alone or in combination with dopamine

15、 D1 (SCH 39166) or D2(eticlopride) receptor antagonists as reported: saline+Rotigotine (0.035 mg/kg s.c., n=9; 0.1 mg/kg s.c., n=9; 0.35mg/kg s.c., n=8); SCH 39166 (0.1 mg/kg s.c.)+Rotigotine (0.035 mg/kg s.c., n=5; 0.1 mg/kg s.c., n=7; 0.35 mg/kg s.c.,n=5); eticlopride (0.1 mg/kg s.c.) + Rotigotine

16、 (0.1 mg/kg s.c., n=5; 0.35 mg/kg s.c., n=5); Saline+pramipexole (0.035Page 2 of 3 www.MedChemEmg/kg s.c., n=5; 0.1 mg/kg s.c., n=12; 0.35 mg/kg s.c., n=7); SCH 39166 (0.1 mg/kg s.c.)+pramipexole (0.035 mg/kgs.c., n=5; 0.1 mg/kg s.c., n=6; 0.35 mg/kg s.c., n=6); eticlopride (0.1 mg/kg s.c.)+pramipex

17、ole (0.1 mg/kg s.c., n=7; 0.35mg/kg s.c., n=5).MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Clin Chem. 2019 Dec;65(12):1522-1531.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Wood M, et al. Rotigotine is

18、 a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors. Br J Pharmacol. 2015Feb;172(4):1124-35.2. Scheller D, et al. The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinsons disease. Naunyn Schmiedebergs Arch Pharmacol.2009 Jan;379(1):73-86.3. Fenu S, et al. In vivo dopamine agonist properties of rotigotine: Role of D1 and D2 receptors. Eur J Pharmacol. 2016 Oct 5;788:183-91.4. Radad K, et al. Neuroprotective effect of rotigotine against complex I inhibitors, MPP? and rotenone, in primary