| Size | Price | Stock | Qty |
|---|---|---|---|
| 2g |
|
||
| 5g |
|
||
| 10g |
|
||
| 50g |
|
||
| 100g |
|
||
| Other Sizes |
Purity: ≥98%
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.
| Targets |
Cannabinoid Receptor Type 1 (CB1): Pregnenolone is hypothesized to antagonize CB1 (mediating cannabis intoxication protection) [1]
|
|---|---|
| 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].
1. Protection Against Cannabis Intoxication in Mice ([1]): Female C57BL/6 mice (8–10 weeks old) received intraperitoneal injection of Pregnenolone (10 mg/kg) 30 minutes before cannabis extract (Δ⁹-THC, 5 mg/kg, intraperitoneal). Pregnenolone significantly improved Δ⁹-THC-induced motor incoordination: rotarod latency increased by 65% (vs. Δ⁹-THC alone) and open-field locomotor activity recovered by 50% (video tracking). It also reversed Δ⁹-THC-induced memory impairment: novel object recognition index increased from 35% (Δ⁹-THC alone) to 65% (with Pregnenolone) [1] 2. Brain Distribution and Behavioral Effects in Rats ([2]): Male Wistar rats (250–300 g) received Pregnenolone via intranasal (10 mg/kg) or intravenous (5 mg/kg) administration. - Brain Distribution: Intranasal administration resulted in peak brain concentration (1.2 μg/g tissue) at 30 minutes, while intravenous administration reached 0.8 μg/g at 15 minutes. Brain/plasma concentration ratio was 2.1 (intranasal) vs. 1.3 (intravenous) [2] - Behavioral Effects: Intranasal Pregnenolone (10 mg/kg) increased exploratory behavior (hole-board test: 40% more head-dips vs. vehicle) without affecting anxiety (elevated plus-maze: no change in open-arm time) [2] |
| Animal Protocol |
Adult male Wistar rats (weighing 320-340g), Sprague Dawley male rats (weighing 330-350g), C57BL/6N mice (2-3 months) and CD1 mice (weighing 25-30 g at the beginning of the experiments) are used. Pregnenolone is injected subcutaneously (sc). The injection volumes are 1 mL/kg of body weight for rats and 10 mL/kg for mice
Mice and rats 1. Mouse Cannabis Intoxication Protection Protocol ([1]): - Animal Selection: 8–10 weeks old female C57BL/6 mice (n=8/group) randomized to control, Δ⁹-THC alone, Δ⁹-THC + Pregnenolone. - Drug Preparation: Pregnenolone dissolved in ethanol (10%) + normal saline (90%) to 1 mg/mL; Δ⁹-THC dissolved in sesame oil to 0.5 mg/mL. - Administration: Pregnenolone (10 mg/kg, 10 mL/kg volume) administered via intraperitoneal injection 30 minutes before Δ⁹-THC (5 mg/kg, 10 mL/kg volume, intraperitoneal). - Detection: Behavioral tests conducted 1 hour post-Δ⁹-THC: rotarod (motor coordination), open-field (locomotion), novel object recognition (memory) [1] 2. Rat Brain Distribution & Behavior Protocol ([2]): - Animal Selection: 250–300 g male Wistar rats (n=6/group) randomized to intranasal Pregnenolone, intravenous Pregnenolone, vehicle. - Drug Preparation: 1. Intranasal: Pregnenolone suspended in 20% hydroxypropyl-β-cyclodextrin (HPβCD) to 10 mg/mL. 2. Intravenous: Pregnenolone dissolved in normal saline to 5 mg/mL. - Administration: 1. Intranasal: 10 mg/kg (1 mL/kg volume) via nasal drops (50 μL/nostril). 2. Intravenous: 5 mg/kg (1 mL/kg volume) via tail vein injection. - Detection: 1. Brain Distribution: Rats euthanized at 0.5, 1, 2, 4 hours post-administration; brain tissue homogenized, Pregnenolone quantified via HPLC. 2. Behavior: Hole-board test (exploration) and elevated plus-maze (anxiety) conducted 1 hour post-intranasal administration [2] |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Known human metabolites of pregnenolone include 1-(3,16-dihydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecano-1H-cyclopenta[a]phenanthrene-17-yl) acetone, 2-hydroxy-1-(3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecano-1H-cyclopenta[a]phenanthrene-17-yl) acetone, and pregn-5-en-20-one-3β-yl sulfate. Brain distribution: 1. Intranasal administration (10 mg/kg, rat): peak brain concentration was 1.2 μg/g (30 min), brain/plasma ratio was 2.1, elimination half-life (t1/2) was 1.8 h[2] 2. Intravenous administration (5 mg/kg, rat): peak brain concentration was 0.8 μg/g (15 min), brain/plasma ratio was 1.3, t1/2 was 1.5 h[2] -Absorption: the bioavailability of pregnenolone administered intranasally in rats was approximately 35% (100% for intravenous administration)[2] |
| References |
|
| Additional Infomation |
Pregnenolone is a 20-oxosteroid with the structure pregn-5-ene, substituted with a β-hydroxyl group at position 3 and an oxo group at position 20. It is a metabolite in both humans and mice. It is a 20-oxosteroid, a C21 steroid, and a 3β-hydroxy-Δ5 steroid. It is derived from the hydride of pregnane. A 21-carbon steroid derived from cholesterol, it is found in tissues that produce steroid hormones. Pregnenolone is a precursor to gonadal steroid hormones and adrenocortical hormones. Pregnenolone has been reported in the Abedus herberti locust, the migratory locust (Locusta migratoria), and other organisms with relevant data.
Pregnenolone is an endogenous steroid hormone synthesized from cholesterol. It can function as a neuroactive steroid and as a precursor hormone for progestins, mineralocorticoids, glucocorticoids, androgens, estrogens, and neuroactive steroids. It is a 21-carbon steroid derived from cholesterol and found in tissues that produce steroid hormones. Pregnenolone is a precursor to gonadal steroid hormones and adrenocortical hormones. 1. Drug Background ([1][2]): Pregnenolone is an endogenous steroid precursor synthesized by the adrenal cortex, brain, and gonads. It is a precursor to progesterone, androgens, and estrogens and has neuroprotective effects [1][2]. 2. Mechanism of Action ([1]): Pregnenolone may prevent cannabis intoxication by antagonizing the CB1 receptor (a major central target of cannabis), but there is a lack of evidence for direct binding. It does not affect the concentration of Δ⁹-THC in plasma, indicating that it acts on the central nervous system [1] 3. Advantages of the route of administration ([2]): Intranasal administration of pregnenolone has better brain targeting (higher brain/plasma concentration ratio) than intravenous administration, making it a potential route for neuroprotective therapy [2] |
| 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
|
|
| 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 |
|
|
| 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 |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| 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. View More
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. 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. |
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA