SKF83959

SKF83959用途

SKF83959是一种有效的选择性多巴胺D1样受体部分激动剂。大鼠D1、D5、D2和D3受体的SKF83959 Ki值分别为1.18、7.56、920和399 nM。SKF83959是西格玛(σ)-1受体的有效变构调节剂。SKF83959属于苯扎地平家族,对认知功能障碍有改善作用。SKF83959可用于阿尔茨海默病和抑郁症的研究[1][2][3][4]。

SKF83959名称

[ CAS 号 ]:
80751-85-5

[ 英文名 ]:
SKF 83959 HYDROBROMIDE

[英文别名 ]:

SKF83959生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 多巴胺受体

信号通路 >> 神经信号通路 >> 多巴胺受体

研究领域 >> 神经疾病

信号通路 >> G 蛋白偶联受体/G 蛋白 >> Sigma Receptor

[ 靶点 ]

D1 Receptor:1.18 nM (Ki)

D5 Receptor:7.56 nM (Ki)

D2 Receptor:920 nM (Ki)

D3 Receptor:399 nM (Ki)

Sigma (σ)-1

[体外研究]

SKF83959(10~250μM)刺激膜中PIP2水解。SKF83959(0.1~10μM；PC12细胞)将对照组织中SKF81297的EC50值从0.5 nM改变为31.6 nM、251.2 nM和631.0 nM[2]。

[体内研究]

SKF83959(0.5和1 mg/kg；i、 p。；1小时)逆转被动回避任务和Y-迷宫测试中东莨菪碱引起的认知损害[1]。SKF83959(1毫克/千克；i、 p。；脑源性神经营养因子系统阻断可阻止诱导的记忆增强效应[1]。SKF83959具有抗健忘症活性,可恢复小鼠海马中东莨菪碱减少的BDNF信号通路[1]。动物模型：雄性ICR雄性小鼠(8周)[1]剂量：0.5和1mg/kg给药：腹腔注射。；1小时结果：在被动回避任务和Y-迷宫测试中逆转东莨菪碱诱导的认知损害。动物模型：雄性ICR雄性小鼠(8周)[1]剂量：1mg/kg给药：腹腔注射。；结果：脑源性神经营养因子(BDNF)系统阻断可抑制记忆增强效应。

[参考文献]

[1]. Sheng G, et al. SKF83959 Has Protective Effects in the Scopolamine Model of Dementia. Biol Pharm Bull. 2018;41(3):427-434.

[2]. Jin LQ, et al. SKF83959 selectively regulates phosphatidylinositol-linked D1 dopamine receptors in rat brain. J Neurochem. 2003;85(2):378-386.

[3]. Neumeyer JL, et al. Receptor affinities of dopamine D1 receptor-selective novel phenylbenzazepines. Eur J Pharmacol. 2003;474(2-3):137-140.

[4]. Guo L, et al. SKF83959 is a potent allosteric modulator of sigma-1 receptor. Mol Pharmacol. 2013;83(3):577-586.

SKF83959物理化学性质

[ 密度 ]:
1.249g/cm3

[ 沸点 ]:
464.6ºC at 760 mmHg

[ 分子式 ]:
C₁₈H₂₁BrClNO₂

[ 分子量 ]:
398.72200

[ 闪点 ]:
234.8ºC

[ 精确质量 ]:
397.04400

[ PSA ]:
43.70000

[ LogP ]:
4.57540

[ 折射率 ]:
1.619

SKF83959MSDS

详细MSDS(安全技术说明书)

SKF83959安全信息

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 危险品运输编码 ]:
NONH for all modes of transport

SKF83959文献

SKF83959 is a potent allosteric modulator of sigma-1 receptor.

Mol. Pharmacol. 83(3) , 577-86, (2013)

SKF83959 (3-methyl-6-chloro-7,8-hydroxy-1-[3-methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine), an atypical dopamine receptor-1 (D(1) receptor) agonist, has shown many D(1) receptor-independent effec...

The D₁ dopamine receptor agonist, SKF83959, attenuates hydrogen peroxide-induced injury in RGC-5 cells involving the extracellular signal-regulated kinase/p38 pathways.

Mol. Vis. 18 , 2882-95, (2012)

Oxidative stress is widely implicated in the death of retinal ganglion cells associated with various optic neuropathies. Agonists of the dopamine D(1) receptor have recently been found to be potential...

Phosphatidylinositol-linked novel D(1) dopamine receptor facilitates long-term depression in rat hippocampal CA1 synapses.

Neuropharmacology 57(2) , 164-71, (2009)

Recent work has demonstrated that a phosphatidylinositol (PI)-linked D(1) dopamine receptor selective agonist, SKF83959, mediates phosphatidylinositol hydrolysis via activation of phospholipase C(beta...

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