利鲁唑作用机制 - Medchemexpress - MCE中国

1、Product Data SheetRiluzoleCat. No.: HY-B0211CAS No.: 1744-22-5分式: CHFNOS分量: 234.2作靶点: Sodium Channel; GABA Receptor作通路: Membrane Transporter/Ion Channel; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (426.99 mM; Need ultrasonic)H2O

2、 : 1 mg/mL (4.27 mM; ultrasonic and adjust pH to 3 with HCl)SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 4.2699 mL 21.3493 mL 42.6985 mL5 mM 0.8540 mL 4.2699 mL 8.5397 mL10 mM 0.4270 mL 2.1349 mL 4.2699 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 mo

3、nth。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (10.67

4、 mM); Clear solution此案可获得 2.5 mg/mL (10.67 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (10.67 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2

5、.5 mg/mL (10.67 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (10.67 mM); Clear solution此案可获得 2.5 mg/mL (10.67 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油

6、中，混合均匀。BIOLOGICAL ACTIVITY物活性 Riluzole种抗惊厥药物，属于依赖于使的钠通道阻滞剂家族，它也可以抑制 GABA 摄取，其 IC50 值为 43 M。IC & Target Sodium channel1IC50: 43 M (GABA receptor)1体外研究 Riluzole is an anticonvulsant drug and belongs to the family of use-dependent Na+ channel blocker which can alsoinhibit GABA uptake with an IC50 of 43

7、 M. At 20 M, Riluzole inhibits peak autaptic IPSCs only slightly but prolongsIPSCs reliably. It is also found that Riluzole causes a strong, concentration-dependent, readily reversible enhancementof responses to 2 M GABA. At higher concentrations of Riluzole, especially 300 M, GABA currents exhibit

8、apparentdesensitization during prolonged co-exposure to 2 M GABA and Riluzole. The EC50 of Riluzole potentiation of GABAresponses is about 60 M1.体内研究 In normal nave rats, systemic injection of Riluzole (8 mg/kg, i.p.; n=6 rats) decreases the duration of ultrasonic butnot audible vocalizations evoked

9、 by noxious stimulation of the knee joint compare to vehicle tested in the same rats(P0.05). Systemic application of Riluzole (8 mg/kg, i.p.; n=19 rats) decreases the vocalizations of arthritic ratscompare to predrug and vehicle significantly (P0.05 to 0.001). Riluzole administered into the CeA sign

10、ificantlydecreases the duration of audible and ultrasonic vocalizations evoked by noxious stimulation of the knee compare topredrug values (n=8 rats; P0.05 to 0.01)2.PROTOCOLCell Assay 1 Two-electrode voltage clamp of Xenopus oocytes expressing exogenous GABAA receptors is performed with a CA-1Bhigh

11、 performance oocyte clamp. The extracellular recording solution is ND-96 medium. Riluzole is applied from acommon tip via a gravity-driven multibarrel drug-delivery system. Data acquisition and analysis are performed withpCLAMP 6 software1.MCE has not independently confirmed the accuracy of these me

12、thods. They are for reference only.Animal Adult male Sprague-Dawley rats (180 to 350 g) are housed in a temperature-controlled room and maintained on aAdministration 2 12-h day/night cycle with unrestricted access to food and water. Pain behaviors are measured before and 5 h afterinduction of a mono

13、-arthritis in the left knee joint. To test the effects of systemic (intraperitoneal, i.p.) application ofRiluzole, pain behaviors are measured 1 h postinjection of Riluzole in normal and arthritic animals. To determineeffects of Riluzole into the amygdala, pain behaviors are measured 15 min after st

14、arting Riluzole application througha stereotaxically implanted microdialysis probe. To investigate site of action in the amygdala of systemically appliedRiluzole, potassium channel blockers are administered into the amygdala 45 min after systemic application ofRiluzole and pain behaviors are measure

15、d 15 min later, i.e., 1 h postinjection of riluzole (i.p.)2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemE户使本产品发表的科研献 Pharmacol Biochem Behav. 2018 May;168:43-50.See more customer validations on HYPERLINK www.MedChemE www.MedCh

16、emEREFERENCES1. He Y, et al. Neuroprotective agent riluzole potentiates postsynaptic GABA(A) receptor function. Neuropharmacology. 2002 Feb;42(2):199-209.2. Thompson JM, et al. Small-conductance calcium-activated potassium (SK) channels in the amygdala mediate pain-inhibiting effects of clinically availableriluzole in a rat model of arthritis pain. Mol Pa