酮色林作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetKetanserinCat. No.: HY-10562CAS No.: 74050-98-9分式: CHFNO分量: 395.43作靶點(diǎn): 5-HT Receptor; Potassium Channel; Autophagy作通路: GPCR/G Protein; Neuronal Signaling; Membrane Transporter/Ion Channel;Autophagy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

2、: 16.67 mg/mL (42.16 mM; Need ultrasonic)DMF : 5 mg/mL (12.64 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.5289 mL 12.6445 mL 25.2889 mL5 mM 0.5058 mL 2.5289 mL 5.0578 mL10 mM 0.2529 mL 1.2644 mL 2.5289 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

3、, 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)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% DMF 40% PEG300 5% Tween-80 45% saline2.Solub

4、ility: 0.5 mg/mL (1.26 mM); Clear solution請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 1.67 mg/mL (4.22 mM); Clear solution此案可獲得 1.67 mg/mL (4.22 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 16.699999 mg/mL 的澄清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

5、。Page 1 of 2 www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1.67 mg/mL (4.22 mM); Clear solution此案可獲得 1.67 mg/mL (4.22 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 16.699999 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。4. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 1.67 mg/mL (

6、4.22 mM); Clear solution此案可獲得 1.67 mg/mL (4.22 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 16.699999 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Ketanserin種選擇性的 5-HT receptor 拮抗劑。Ketanserin 也抑制hERG電流 (IhERG)，IC50 為 0.11 M，這種作具有濃度依賴性。IC & Target serotonin hERG current150 M (IC

7、50) 0.11 M (IC50)體外研究 Ketanserin at 0.3 M inhibits the voltage-dependent step current (IhERG.step) and tail current (IhERG.tail) of hERGchannels with a 5-min exposure1. The synergistic effect observed for AA with 5-HT is, also, blocked by the 5-HTreceptor blockers cyproheptadine (IC50=22.07 M), Keta

8、nserin (IC50=15223 M). Ketanserin (50-350 M) inhibitsthe synergism by blocking the receptor in a dose-dependent manner. The IC50 value of Cyproheptadine is 227 Mand Ketanserin is 15223 M2. Ketanserin inhibits platelet aggregation with an IC50 of 240 (169-339) nM3.體內(nèi)研究 Ketanserin is a 5-HT2A receptor

9、 antagonist. Ketanserin significantly reduces BDNF protein levels in numerous brain regions (CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and midbrain periaqueductal gray). 5-HT2A antago

10、nistKetanserin can significantly reduce BDNF mRNA levels in various brain regions4.PROTOCOLCell Assay 1 The established HEK 293 cell line stably expressing hERG channels is cultured in Dulbeccos modified Eagles medium(DMEM) supplemented with 10% foetal bovine serum, 400 g/mL G418. The HEK 293 cell l

11、ine stably expressingrecombinant human cardiac KCNQ1/KCNE1 channel current (IKs) is maintained in DMEM containing 10% foetalbovine serum and 100 g/mL hygromycin. Cells used for electrophysiology are seeded on a glass coverslip. Themutant hERG channels are constructed, and are transiently expressed i

12、n HEK 293 cells using 10 L of Lipofectamine2000 with 4 g of hERG mutant cDNA in pCDNA3 vector1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rat4Administration 4 A total of 155 specific-pathogen-free 2-month-old male Sprague-Dawley rats, weighi

13、ng 180-220 g, are used. The ratsare randomly divided into the following six groups: 5-HT1A receptor agonist (8-OH-DPAT) PS group (DPAT-PS group,n=30); 5-HT1A receptor antagonist (MDL73005) PS group (MDL-PS group, n=30); 5-HT2A receptor agonist (DOI) PSgroup (DOI-PS group, n=30); 5-HT2A receptor anta

14、gonist (Ketanserin) PS group (Ketan-PS group, n=30); the solventcontrol no-stress group (0.9% physiological saline group, CON group); and the PS only group (PS group, n=30). TheDPAT-PS, MDL-PS, DOI-PS, Ketan-PS and PS groups are further divided into six subgroups (n=5 each) according toPage 2 of 3 w

15、ww.MedChemEthe time between the stress and analysis; immediately after stress, and 0.5, 1, 2, 6 and 24 hours after stress. The CONgroup (n=5) receive normal feed. For the Ketan-PS group, Ketanserin, dissolved in 0.9% physiological saline, isinjected intraperitoneally at 5 mg/kg at 1 hour before each

16、 stress exposure.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Tang Q, et al. The 5-HT2 antagonist Ketanserin is an open channel blocker of human cardiac ether-go-go-related gene (hERG) potassium channels. BrJ Pharmacol. 2008 Oct;155(3):3

17、65-73.2. Khan N, et al. Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction ofvarious agonists. Drug Des Devel Ther. 2015 Jul 6;9:3497-506.3. Kekewska A, et al. Antiserotonergic properties of terguride in blood vessels, platelets, and valvular interstitial cells. J Pharmacol Exp Ther. 2012Feb;340(2):369-76.4. Jiang DG, et al. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological str