Rapacuronium-bromide-Org-9487-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERapacuronium bromideCat. No.: HY-16423CAS No.: 156137-99-4Synonyms: Org 9487分式: CHBrNO分量: 677.8作靶点: mAChR作通路: GPCR/G Protein; Neuronal Signaling储存式: Powder -20C 3 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 125 mg/

2、mL (184.42 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.4754 mL 7.3768 mL 14.7536 mL5 mM 0.2951 mL 1.4754 mL 2.9507 mL10 mM 0.1475 mL 0.7377 mL 1.4754 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，并请注意储备液的保存式和期限。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，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证

3、实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (3.07 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (3.07 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 9

4、0% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.08 mg/mL (3.07 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Rapacuronium bromide种毒蕈碱性酰胆碱受体 (mAChR) 的变构调节剂。IC50 & Target Muscarinic receptor 1体外研究 Rapacuronium binds to all muscarinic receptor subtypes at physiologically relevant

5、concentrations anddisplays micromolar affinity and slight selectivity towards M2 receptor. Rapacuronium exhibits complexeffects on the kinetics of ACh binding and subsequent receptor activation estimated from stimulation of35SGTPS binding. Rapacuronium alone concentration dependently lowers 35SGTPS

6、binding tomembranes with a maximal effect of approximately 25% at odd-numbered subtypes and 15% at even-numbered subtypes, with EC50 ranging from 28 M at M2 receptors to 76 M at M3 receptors. While theEC50 values of Rapacuronium in inhibiting 35SGTPS binding at individual subtypes correlated withaff

7、inities measured in binding experiments with 3HACh (R2 = 0.76) they are lower (4- to 12-fold) at allsubtypes. Measurements of ACh-stimulated 35SGTPS binding in the presence of 0.1, 1 and 10 MRapacuronium shows differential effects of Rapacuronium on receptor activation by an orthosteric agonist atin

8、dividual receptor subtypes. At even-numbered subtypes 1 M and 10 M Rapacuronium significantlyincreases ACh EC50, with lowering of EMAX at 10 M Rapacuronium. At this subtype 0.1 and 1 MRapacuronium causes a significant 2-fold decrease in ACh EC50 and approximately 60% and 35% increasein EMAX, respect

9、ively. Rapacuronium at 10 M increases ACh EC50 by about 3-fold without a significantchange in EMAX. Rapacuronium (0.1 - 10 M) has no effect on ACh efficacy at the M1 and M5 subtypes butdecreases the EC50 of ACh in stimulating 35SGTPS binding by 1.5- and 4-fold, respectively, atconcentrations of 0.1

10、and 1 M. However, this effect is not evident at 10 M Rapacuronium 1.体内研究 Time course of the neuromuscular effects of Rapacuronium following the administration of the 2ED90 dosesto rats and guinea-pigs with ED90 of 5953199 and 18716 g/kg in rat and guinea pig, respectively 2.PROTOCOLKinase Assay 1 Fo

11、r determination of 35SGTPS binding to G-proteins in membranes a final concentration of 200 pM (M1,M3 and M5 receptors) or 500 pM (M2 and M4 receptors) of 35SGTPS is used. Incubation medium issupplemented with 5 M (M1, M3 and M5 receptors) or 50 M (M2 and M4 receptors) GDP. Nonspecificbinding is dete

12、rmined in the presence of 1 M unlabeled GTPS. When effects of Rapacuronium on ACh-stimulated 35SGTPS binding is measured Rapacuronium is added to membranes 60 min prior to ACh and35SGTPS. Incubation with 35SGTPS is carried out for 20 min and free ligand is removed by filtration asdescribed above. Fi

13、ltration and washing with ice-cold water lasted for 9 s (wash-aspirate button time). Afterfiltration filters are dried in vacuum for 1 h while heated at 80C and then solid scintillator Meltilex A is meltedon filters (105C, 90 s) using a hot plate. After cooling the filters are counted using a Wallac

14、 Microbetascintillation counter 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEREFERENCES1. Jakubk J, et al. Divergence of allosteric effects of Rapacuronium on binding and function of muscarinic receptors. BMC Pharmacol.2009 Dec 28;9:15.2. Vizi ES, et al. A new short-acting non-depolarizing muscle relaxant (SZ1677) without cardiovascular side-effects. Acta AnaesthesiolScand. 2003