GYKI53655-hydrochloride - iGluR Antagonist - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGYKI53655 hydrochlorideCat. No.: HY-103228CAS No.: 143692-48-2分式: CHClNO分量: 388.85作靶点: iGluR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

2、 DMSO : 160 mg/mL (411.47 mM)H2O : 8 mg/mL (20.57 mM; Need ultrasonic and warming)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.5717 mL 12.8584 mL 25.7169 mL5 mM 0.5143 mL 2.5717 mL 5.1434 mL10 mM 0.2572 mL 1.2858 mL 2.5717 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

3、液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 GYKI53655 hydrochloride是-氨基-3-羟基-5-甲基异恶唑-4-丙酸 (AMPA) 的拮抗剂。IC50 & Target AMPA 1体外研究GYKI53655 hydrochloride (LY300168) inhibits -amino-3-hydroxy-5-methylisoxazole-4-propionic acid1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE(AMPA) (10 M)-induced responses wi

4、th IC50 value of 5.90.1 M. GYKI53655 hydrochloride inhibits AMPA(10 M) responses inrecombinant G1uR4 expressing HEK293 cells with IC50 value of 4.60.4 M. Using 3 M cyclothiazide the inhibition produced by GYKI53655 hydrochloride is 792% (n=4 cells). GYKI53655hydrochloride produces only small inhibit

5、ions of kainate-induced currents at 30 M and inhibits kainate-induced currents at a concentration of 100 M by 122 (n=4) and 184 (n=4), respectively. GYKI53655hydrochloride inhibits AMPA receptor-mediated responses in cerebella Purkinje neurons with an IC50 valueof 1.50.1 M 1.体内研究 GYKI53655 hydrochlo

6、ride (4 mg/kg) is found to have a short-lasting depressant effect on neuronal responsesto iontophoretic-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), with a half-recovery time ofapproximately 7 min. GYKI53655 hydrochloride (4 and 8 mg/kg) substantially depresses or completelyabolishes A

7、MPA responses. Results demonstrate the dose-dependence of GYKI53655 hydrochloride (2 to 8mg/kg) in depressing responses to AMPA. At the highest doses tested, GYKI53655 hydrochloride reducesAMPA responses to a comparable degree 2. Tonic fit and death are completely prevented by GYKI53655hydrochloride

8、 at dose over 5.0 mg/kg. The ED50 value of GYKI53655 hydrochloride is 2.2 mg/kg i.p. Themaximal effects of GYKI53655 hydrochloride lasts 3 h then the exit inhibition effect of GYKI53655hydrochloride falls to 20% 1 h later 3.PROTOCOLCell Assay 1 Whole-cell voltage clamp recordings are made from singl

9、e cells with use of the tight seal whole cellconfiguration of the patch-clamp technique. Experiments are performed at room temperature (20 to 22C)and recorded on an amplifier. GYKI53655 hydrochloride application is via a series of perfusion lines to amulti-barrelled applicator and exchange of soluti

10、ons under the present recording conditions is approximately100 msec. For the acutely isolated cerebella Purkinje neurons, GYKI53655 hydrochloride application is bybath perfusion and occurs within approximately 15 sec. Curve fitting to data points is based upon theequationy=100(Dn/(Dn+IC50n), where t

11、he slope of the line n is fixed to a value of 1 and D is the antagonistconcentration. Statistical significance is determined by one-way ANOVA followed by Student- Newman-Keulstest 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Experiments are

12、performed on 27 male Wistar rats (260 to 350 g). Briefly, rats are anaesthetized withAdministration 2 halothane in O2 and tracheal, carotid and jugular cannulae are inserted. The lumbo-thoracic spinal cord isexposed and cut at T9-T11 and the animal is prepared for extracellular recordings of single

13、dorsal hornneurone action potentials. Anaesthesia after surgery is maintained with -chloralose. Jugular cannulae areinserted. GYKI53655 hydrochloride is administered intravenously. The effect of GYKI53655 hydrochloride isexpressed quantitatively as percentages of control excitatory amino acids (EAA)

14、 responses, where control istaken as the mean of the last 3 pre-drug counts; mean valuess.e.mean are indicated. No corrections forspontaneous activity are made 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Molecules 您边的

15、抑制剂师www.MedChemE1. Bleakman D, et al. Activity of 2,3-benzodiazepines at native rat and recombinant human glutamate receptors in vitro: stereospecificityand selectivity profiles. Neuropharmacology. 1996;35(12):1689-702.2. Chizh BA, et al. A comparison of intravenous NBQX and GYKI 53655 as AMPA antagonists in the rat spinal cord. Br J Pharmacol. 1994Jul;112(3):843-6.3. Szabados T, et al. Comparison of anticonvulsive and acute neuroprotective activity of three 2,3-benzodiazepine compounds, GYKI52466, GYKI 53405, and GYKI 53655. B