CAS 516-54-1|5alpha-Pregnan-3alpha-ol-20-one
| Common Name | 5alpha-Pregnan-3alpha-ol-20-one | ||
|---|---|---|---|
| CAS Number | 516-54-1 | Molecular Weight | 318.493 |
| Density | 1.1±0.1 g/cm3 | Boiling Point | 431.2±18.0 °C at 760 mmHg |
| Molecular Formula | C21H34O2 | Melting Point | 176-178° |
| MSDS | USA | Flash Point | 183.9±13.8 °C |
Names
| Name | 3α-hydroxy-5α-pregnan-20-one |
|---|---|
| Synonym | More Synonyms |
5alpha-Pregnan-3alpha-ol-20-one BiologicalActivity
| Description | Allopregnanolone is a progesterone metabolite. Allopregnanolone is an allosteric modulator of the GABA receptor. |
|---|---|
| Related Catalog | Signaling Pathways >>Membrane Transporter/Ion Channel >>GABA ReceptorSignaling Pathways >>Neuronal Signaling >>GABA ReceptorNatural Products >>SteroidsResearch Areas >>Neurological Disease |
| Target | Human Endogenous Metabolite |
| In Vitro | Allopregnanolone induces a significant increase in proliferation of neuroprogenitor cells derived from the rat hippocampus and human neural stem cells derived from the cerebral cortex in a dose-dependent manner. Allopregnanolone increases the expression of genes that promote mitosis and inhibits the expression of genes that repress cell proliferation[1]. Its biosynthesis begins with progesterone, which is converted to dihydroprogesterone by the enzyme 5α-DHP and after that, the enzyme 3α-HSOR catalyses the reduction of dihydroprogesterone toward allopregnanolone[2] |
| In Vivo | Allopregnanolone increases both the K+-evoked [3H]-glutamate and [3H]-GABA release in P rats. The neurosteroid also increases the basal release of [3H]-glutamate in VO rats in an effect that is dependent on the modulation of NMDA receptors as is reverted by Mg2+[2]. At therapeutic doses by either subcutaneous or intravenous routes, allopregnanolone mouse plasma levels range between 34-51ng/mL by 30min[3]. Allopregnanolone-induced neurogenesis correlates with restoration of learning and memory function in a mouse model of Alzheimer's disease and is comparably efficacious in aged normal mice[4]. Progesterone and allopregnanolone has shown neuroprotective effects in different experimental models including stroke and spinal cord injury[5]. |
| Animal Admin | Rats: Allopregnanolone is dissolved in propylenglycol to a concentration of 0.6 mM and diluted in Krebs Ringer bicarbonate glucose (KRBG) Mg2+-free buffer at pH 7.4 to 120 nM. To antagonize GABA receptors, 120 nM allopregnanolone plus 9.8 μM Bic (Bic+Allo groups) or 9.8 μM Bic alone (Bic groups) is used[2]. Mice: Allopregnanolone is dissolved in 20%w/v HBCD solution at 2.5 mg/mL by brief sonication and is subcutaneously (SC) injected to mice at 0.5, 1, and 10 mg/kg. Additionally, allopregnanolone is dissolved in 6%w/v SBECD solution at 0.5 mg/mL and injected IV to mice at 0.1, 0.5, and 1 mg/kg. HBCD or SBECD alone are included as vehicle controls. Topical transdermal is applied on the shaved dorsal surface at 50mg/kg using a gel solution of 3.3% allopregnanolone (w/w), 45% DMSO, 30% EtOH, 2.5% Klucel MF, 19.2% PEG-300. Intranasal formulations are prepared in both 100% castor oil and 20% HBCD. Intramuscular formulation is administered to mice as allopregnanolone 1.5 mg/mL in 6% SBECD[3]. |
| References | [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. |
Chemical & Physical Properties
| Density | 1.1±0.1 g/cm3 |
|---|---|
| Boiling Point | 431.2±18.0 °C at 760 mmHg |
| Melting Point | 176-178° |
| Molecular Formula | C21H34O2 |
| Molecular Weight | 318.493 |
| Flash Point | 183.9±13.8 °C |
| Exact Mass | 318.255890 |
| PSA | 37.30000 |
| LogP | 4.89 |
| Appearance of Characters | White solid |
| Vapour Pressure | 0.0±2.3 mmHg at 25°C |
| Index of Refraction | 1.524 |
| InChIKey | AURFZBICLPNKBZ-SYBPFIFISA-N |
| SMILES | CC(=O)C1CCC2C3CCC4CC(O)CCC4(C)C3CCC12C |
| Storage condition | Store at RT |
| Water Solubility | chloroform: 20 mg/mL, clear, colorless |
Toxicological Information
CHEMICAL IDENTIFICATION |
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
Safety Information
| Personal Protective Equipment | Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter |
|---|---|
| Safety Phrases | 22-24/25 |
| RIDADR | NONH for all modes of transport |
| WGK Germany | 3 |
| RTECS | TU4383000 |
Articles69
More Articles| 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... |
Synonyms
| 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 |
| 3alpha-hydroxy-5alpha-pregnan-20-one |
| MFCD00003677 |
| UNII:S39XZ5QV8Y |
| Pregnanolone II |
| 3alpha-hydroxy-5beta-pregnan-20-one |
| ALLOPREGNAN-3ALPHA-OL-20-ONE |
| Pregnan-20-one,3-hydroxy-, (3a,5b)- |
| Brexanolone |
| Allopregnanolone |
| 3α-Hydroxy-5α-pregnan-20-one |
| 3a-Hydroxy-5a-pregnane-20-one |
| (3α,5α)-3-Hydroxypregnan-20-one |
| 3a-Hydroxy-5a-pregnan-20-one |
| (+)-3a-Hydroxy-5a-pregnan-20-one |
| 3α,5α-Tetrahydroprogesterone |
| 5α-Pregnan-3α-ol-20-one |
| 5alpha-Pregnan-3alpha-ol-20-one |
| (3α)-Allopregnanolone |
| LJPC-0712 |
