5alpha-Pregnan-3alpha-ol-20-one

Names

[ CAS No. ]:
516-54-1

[ Name ]:
5alpha-Pregnan-3alpha-ol-20-one

[Synonym ]:
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

Biological Activity

[Description]:

Allopregnanolone is a progesterone metabolite. Allopregnanolone is an allosteric modulator of the GABA receptor.

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor

Signaling Pathways >> Neuronal Signaling >> GABA Receptor

Natural Products >> Steroids

Research 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.

[Related Small Molecules]

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

[ Storage condition ]:
Store at RT

[ Water Solubility ]:
chloroform: 20 mg/mL, clear, colorless

MSDS

Click to get detail MSDS

Toxicological Information

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

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

Precursor & DownStream

Precursor

DownStream

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...