Pregnenolone (NSC-1616; NSC-18158; Prenolon; Regnosone; Skinostelon; Enelone; Natolone; Pregnetan; Pregneton; Pregnolon) is an endogenous/naturally occurring steroidal hormone that has been used in the treatment of fatigue, Alzheimer's disease, trauma and injuries. It is neurosteroid and a key precursor for the biosynthesis of many steroids including progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens, making it a prohormone. It has been observed to inhibit GABA-gated chloride currents by enhancing receptor desensitization.
Physicochemical Properties
| Molecular Formula | C21H32O2 | |
| Molecular Weight | 316.48 | |
| Exact Mass | 316.24 | |
| CAS # | 145-13-1 | |
| Related CAS # | Pregnenolone monosulfate sodium;1852-38-6;Pregnenolone-d4-1;61574-54-7;Pregnenolone monosulfate;1247-64-9;Pregnenolone-d4;Pregnenolone-13C2,d2;2483824-26-4 | |
| PubChem CID | 8955 | |
| Appearance | White to off-white solid powder | |
| Density | 1.1±0.1 g/cm3 | |
| Boiling Point | 443.3±45.0 °C at 760 mmHg | |
| Melting Point | 188-190 °C | |
| Flash Point | 188.9±21.3 °C | |
| Vapour Pressure | 0.0±2.4 mmHg at 25°C | |
| Index of Refraction | 1.550 | |
| LogP | 4.52 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 2 | |
| Rotatable Bond Count | 1 | |
| Heavy Atom Count | 23 | |
| Complexity | 550 | |
| Defined Atom Stereocenter Count | 7 | |
| SMILES | CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C |
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| InChi Key | ORNBQBCIOKFOEO-QGVNFLHTSA-N | |
| InChi Code | InChI=1S/C21H32O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h4,15-19,23H,5-12H2,1-3H3/t15-,16-,17+,18-,19-,20-,21+/m0/s1 | |
| Chemical Name | 1-((3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one | |
| Synonyms |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | The stimulation of CB1 receptors raises levels of pregnenolone in the brain, which counteracts most of the known behavioral and physical effects of THC by acting as a negative feedback loop on CB1 receptor activity. Pregnenolone most likely binds to a different location than orthosteric ligands, acting as a signaling-specific negative allosteric modulator. Pregnenolone solely affects agonist effectiveness; it has no effect on agonist binding[1]. Applying 100 nM of pregnenolone to slices before to THC treatment considerably reduces its impact (15.11±1.8% of inhibition). Pregnenolone's pre-synaptic activity is most likely the cause of these effects. Pregnenolone thus prevents the paired-pulse ratio (PPR) from increasing as a result of THC, but it has no effect on the amplitude or decay time of the miniature EPSC (mEPSC)[1]. | ||
| ln Vivo | Administering pregnenolone (2–6 mg/kg) blunts the memory impairment caused by THC in mice and prevents THC-induced food intake in Wistar rats and C57BL/6N mice, but it does not change these behaviors in and of themselves. Pregnenolone injections (2 and 4 mg/kg) prior to each self-administration session lower WIN 55,212-2 intake and lower the progressive ratio schedule's break-point[1]. | ||
| Animal Protocol |
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| ADME/Pharmacokinetics |
Metabolism / Metabolites Pregnenolone has known human metabolites that include 1-(3,16-Dihydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethanone, 2-Hydroxy-1-(3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethanone, and Pregn-5-en-20-on-3b-yl sulfurate. |
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| References |
[1]. Pregnenolone can protect the brain from cannabis intoxication. Science. 2014 Jan 3;343(6166):94-8. [2]. Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration. Eur J Pharmacol. 2010 Sep 1;641(2-3):128-34. [3]. Alan Shiels. TRPM3_miR-204: a complex locus for eye development and disease. Hum Genomics. 2020 Feb 18;14(1):7. |
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| Additional Infomation |
Pregnenolone is a 20-oxo steroid that is pregn-5-ene substituted by a beta-hydroxy group at position 3 and an oxo group at position 20. It has a role as a human metabolite and a mouse metabolite. It is a 20-oxo steroid, a C21-steroid and a 3beta-hydroxy-Delta(5)-steroid. It derives from a hydride of a pregnane. A 21-carbon steroid, derived from cholesterol and found in steroid hormone-producing tissues. Pregnenolone is the precursor to gonadal steroid hormones and the adrenal corticosteroids. Pregnenolone has been reported in Abedus herberti, Locusta migratoria, and other organisms with data available. Pregnenolone is an endogenous steroid hormone synthesized from cholesterol, which can act either as a neuroactive steroid or as a prohormone for progestogens, mineralocorticoids, glucocorticoids, androgens, estrogens, and the neuroactive steroids. A 21-carbon steroid, derived from CHOLESTEROL and found in steroid hormone-producing tissues. Pregnenolone is the precursor to GONADAL STEROID HORMONES and the adrenal CORTICOSTEROIDS. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.90 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 3: 1.25 mg/mL (3.95 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 4: 10 mg/mL (31.60 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1598 mL | 15.7988 mL | 31.5976 mL | |
| 5 mM | 0.6320 mL | 3.1598 mL | 6.3195 mL | |
| 10 mM | 0.3160 mL | 1.5799 mL | 3.1598 mL |