利哌酮作用機制 - Medchemexpress - MCE中國

1、Product Data SheetRisperidoneCat. No.: HY-11018CAS No.: 106266-06-2分式: CHFNO分量: 410.48作靶點: 5-HT Receptor; Dopamine Receptor; P-glycoprotein作通路: GPCR/G Protein; Neuronal Signaling; Membrane Transporter/Ion Channel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 : 1

2、0 mg/mL (24.36 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 2.4362 mL 12.1809 mL 24.3617 mL5 mM 0.4872 mL 2.4362 mL 4.8723 mL10 mM 0.2436 mL 1.2181 mL 2.4362 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，-20

3、C 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?shù)娜芙獍浮Ｒ韵氯芙獍付颊埾劝凑?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，適當保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 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: 1 mg/mL (2.44 mM); Clear solution此案可獲得 1

4、mg/mL (2.44 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 10.0 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: 1 mg/mL (2.44 mM); Clear solution此案可獲得 1 mg/mL (2.44 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 m

5、L 作液為例，取 100 L 10.0 mg/mL 的澄均勻。DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 1 mg/mL (2.44 mM); Clear solution此案可獲得 1 mg/mL (2.44 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 10.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Risperidone 5-

6、HT2 受體的阻斷劑，P-糖蛋 (P-Glycoprotein) 的抑制劑 和 dopamine D2 受體的拮抗劑，其對 5-HT 2A 和 dopamine D2 受體的 Ki 值分別為 4.8，5.9 nM。IC & Target 5-HT2A Receptor dopamine D2 receptor P-Glycoprotein4.8 nM (Ki) 5.9 nM (Ki)體外研究 Risperidone is a serotonin 5-HT2 receptor blocker, P-Glycoprotein inhibitor and potent dopamine D2 rec

7、eptorantagonist, with Kis of 4.8, 5.9 nM for 5-HT2A and dopamine D2 receptor, respectively. Risperidone dose-dependentlyinhibited the release of IL-12 in mature DCs, while the production of IL-10 is dose-dependently increased byRisperidone. A high dose of risperidone can induce TNF- release from mat

8、ure DCs3.體內(nèi)研究 In the first experiment, body weight is found to be slightly but significantly lower in the Risperidone-treated rats as afunction of age. Similar to the first experiment, age-dependent differences in body weight are also observed betweenthe three treatment groups in the second locomoto

9、r experiment. Rats treated with the 3.0 mg/kg dose of Risperidoneweigh less than vehicle-treated rats on postnatal days 35, 38, and 41. The third locomotor experiment involves larger,mixed-sex litters in contrast to the smaller, single-sex litters used in the first two experiments. As noted for the

10、firsttwo experiments, rats treated with Risperidone in the third experiment gain less weight in an age-dependent manner 4.PROTOCOLAnimal Rats4Administration 4 A total of 211 Long-Evans rats (56 females and 155 males) are used. Within each study, three groups of roughlyequal numbers of rats receive i

11、njections of 1.0 mg/kg of Risperidone, 3.0 mg/kg of Risperidone, or the vehicle usedfor the Risperidone solution as a control. In the first experiment, twenty-six male rats (n=9 in the vehicle and 3.0mg/kg Risperidone groups; n=8 in the 1.0 mg/kg Risperidone group) are tested for locomotor activity

12、for 20minutes a day beginning at postnatal day 49 and continuing daily until postnatal day 53. A second experimentdetermined if the locomotor effects of early-life Risperidone treatment persisted well into adulthood. A thirdexperiment ascertains the effects of sex on the locomotor effects of early-l

13、ife Risperidone seen in young adult rats. Inthis experiment, sixty male (n=20 per treatment group) and 56 female (n=19 rats in the vehicle and 3.0 mg/kg dosegroup, n=18 in the 1.0 mg/kg dose group) rats are treated. A fourth experiment assessed reversal learning duringadulthood in rats administered

14、earlylife risperidone. Forty-two male rats (n=14 per treatment group) are treated4.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Nyberg S, et al. 5-HT2 and D2 dopamine receptor occupancy in the living human brain. A PET study with risperi

15、done. Psychopharmacology (Berl).Page 2 of 3 www.MedChemE1993;110(3):265-72.2. Zhu HJ, et al. Risperidone and paliperidone inhibit p-glycoprotein activity in vitro. Neuropsychopharmacology. 2007 Apr;32(4):757-64.3. Chen ML, et al. Risperidone modulates the cytokine and chemokine release of dendritic cells and induces TNF-directed cell apoptosis in neutrophils.Int Immunopharmacol. 2012 Jan;12(1):197-204.4. Bardgett ME, et al. Adult rats treated with risperidone during development are hyperactive. Exp Clin Psychopharmacol. 2013 J