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5alpha-孕甾-3alpha-醇-20-酮

5alpha-孕甾-3alpha-醇-20-酮用途

Allopregnanolone是孕酮代谢物。它是GABA受体的变构调节剂。

5alpha-孕甾-3alpha-醇-20-酮名称

[ CAS 号 ]:
516-54-1

[ 中文名 ]:
5alpha-孕甾-3alpha-醇-20-酮

[ 英文名 ]:
5alpha-Pregnan-3alpha-ol-20-one

[中文别名 ]:

[英文别名 ]:

Pregnan-20-one, 3-hydroxy-, (3α,5α)-
pregnanalone
Pregnan-20-one, 3-hydroxy-, (3α)-
PREGNAN-3A-OL-20-ONE
(+)-3α-Hydroxy-5α-pregnan-20-one
(3α)-3-Hydroxypregnan-20-one
Butabindide oxalate
3α,5α-THP
(3α)-Allopregnanolone
5-Pregnan-3-ol-20-one

5alpha-孕甾-3alpha-醇-20-酮生物活性

[ 描述 ]:

Allopregnanolone是孕酮代谢物。它是GABA受体的变构调节剂。

[ 相关类别 ]:

信号通路 >> 跨膜转运 >> GABA受体

信号通路 >> 神经信号通路 >> GABA受体

天然产物 >> 类固醇

研究领域 >> 神经疾病

[ 靶点 ]

Human Endogenous Metabolite

[体外研究]

Allopregnanolone以剂量依赖性方式诱导源自大鼠海马的神经祖细胞和源自大脑皮层的人神经干细胞的增殖的显着增加。 Allopregnanolone增加促进有丝分裂的基因的表达,并抑制抑制细胞增殖的基因的表达[1]。它的生物合成以黄体酮开始,黄体酮通过5α-DHP酶转化为二氢孕酮,之后,3α-HSOR酶催化二氢孕酮向异丙肾上腺素的还原[2]

[体内研究]

Allopregnanolone增加P大鼠中K +诱发的[3H] -谷氨酸和[3H] -GABA释放。神经甾体还增加VO大鼠中[3H] -谷氨酸的基础释放,其效果取决于受Mg2 +逆转的NMDA受体的调节[2]。通过皮下或静脉途径的治疗剂量,allopregnanolone小鼠血浆水平在34-51ng/mL之间,30min [3]。 Allopregnanolone诱导的神经发生与阿尔茨海默病小鼠模型中学习和记忆功能的恢复相关,并且在老年正常小鼠中相对有效[4]。黄体酮和异丙肾上腺素在不同的实验模型中显示出神经保护作用,包括中风和脊髓损伤[5]。

[动物实验]

大鼠：将Allopregnanolone溶解在丙二醇中至浓度为0.6mM，并在pH7.4至120nM的Krebs Ringer碳酸氢盐葡萄糖（KRBG）无Mg2 +缓冲液中稀释。为了拮抗GABA受体，使用120nM allopregnanolone加9.8μMBic（Bic + Allo组）或9.8μMBicBic（Bic组）[2]。小鼠：通过短暂超声将Allopregnanolone以2.5mg / mL溶解于20％w / v HBCD溶液中，并以0.5,1和10mg / kg皮下（SC）注射给小鼠。另外，将allopregnanolone以0.5mg / mL溶解于6％w / v SBECD溶液中，并以0.1,0.5和1mg / kg静脉内注射给小鼠。仅包含六溴环十二烷或SBECD作为载体对照。使用3.3％allopregnanolone（w / w），45％DMSO，30％EtOH，2.5％Klucel MF，19.2％PEG-300的凝胶溶液以50mg / kg在剃毛的背面上施用局部透皮。鼻内制剂在100％蓖麻油和20％HBCD中制备。肌内注射制剂作为allopregnanolone 1.5 mg / mL在6％SBECD中给予小鼠[3]。

[参考文献]

[1]. Wang JM, et al. The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression. J Neurosci. 2005 May 11;25(19):4706-18.

[2]. Giuliani FA, et al. Allopregnanolone and puberty: modulatory effect on glutamate and GABA release and expression of 3α-hydroxysteroid oxidoreductase in the hypothalamus of female rats. Neuroscience. 2013 Jul 23;243:64-75.

[3]. Irwin RW, et al. Allopregnanolone Preclinical Acute Pharmacokinetic and Pharmacodynamic Studies to Predict Tolerability and Efficacy for Alzheimer’s Disease. PLoS One. 2015 Jun 3;10(6):e0128313.

[4]. Irwin RW, et al. Allopregnanolone as regenerative therapeutic for Alzheimer's disease: translational development and clinical promise. Prog Neurobiol. 2014 Feb;113:40-55.

[5]. Guennoun R, et al. Progesterone and allopregnanolone in the central nervous system: response to injury and implication for neuroprotection. J Steroid Biochem Mol Biol. 2015 Feb;146:48-61.

[相关活性小分子]

5alpha-孕甾-3alpha-醇-20-酮物理化学性质

[ 密度 ]:
1.1±0.1 g/cm3

[ 沸点 ]:
431.2±18.0 °C at 760 mmHg

[ 熔点 ]:
176-178°

[ 分子式 ]:
C₂₁H₃₄O₂

[ 分子量 ]:
318.493

[ 闪点 ]:
183.9±13.8 °C

[ 精确质量 ]:
318.255890

[ PSA ]:
37.30000

[ LogP ]:
4.89

[ 外观性状 ]:
White solid

[ 蒸汽压 ]:
0.0±2.3 mmHg at 25°C

[ 折射率 ]:
1.524

[ 储存条件 ]:
Store at RT

[ 水溶解性 ]:
chloroform: 20 mg/mL, clear, colorless

5alpha-孕甾-3alpha-醇-20-酮MSDS

详细MSDS(安全技术说明书)

5alpha-孕甾-3alpha-醇-20-酮毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TU4383000

CHEMICAL NAME :: 5-alpha-Pregnan-20-one, 3-alpha-hydroxy-

CAS REGISTRY NUMBER :: 516-54-1

BEILSTEIN REFERENCE NO. :: 3211363

LAST UPDATED :: 199709

DATA ITEMS CITED :: 3

MOLECULAR FORMULA :: C21-H34-O2

MOLECULAR WEIGHT :: 318.55

WISWESSER LINE NOTATION :: L E5 B666TJ A1 E1 FV1 OQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 15 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 11,117,1968

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 20 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 11,117,1968

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 7 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 11,117,1968

5alpha-孕甾-3alpha-醇-20-酮安全信息

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

[ 安全声明 (欧洲) ]:
22-24/25

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

[ WGK德国 ]:
3

[ RTECS号 ]:
TU4383000

5alpha-孕甾-3alpha-醇-20-酮上下游产品

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5alpha-孕甾-3alpha-醇-20-酮文献

Combined treatment with diazepam and allopregnanolone reverses tetramethylenedisulfotetramine (TETS)-induced calcium dysregulation in cultured neurons and protects TETS-intoxicated mice against lethal seizures.

Neuropharmacology 95 , 332-42, (2015)

Tetramethylenedisulfotetramine (TETS) is a potent convulsant GABAA receptor blocker. Mice receiving a lethal dose of TETS (0.15 mg/kg i.p.) are rescued from death by a high dose of diazepam (5 mg/kg i...

Chemical genetics reveals a complex functional ground state of neural stem cells.

Nat. Chem. Biol. 3(5) , 268-273, (2007)

The identification of self-renewing and multipotent neural stem cells (NSCs) in the mammalian brain holds promise for the treatment of neurological diseases and has yielded new insight into brain canc...

Combined liquid chromatography-tandem mass spectrometry analysis of progesterone metabolites.

PLoS ONE 10(2) , e0117984, (2015)

Progesterone has a number of important functions throughout the human body. While the roles of progesterone are well known, the possible actions and implications of progesterone metabolites in differe...

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