Pregnenolone

US Previously Marketed

First approved in 1950

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H32O2
Molecular Weight	316.4776
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CC=C4C[C@@H](O)CC[C@]34C

InChI

InChIKey=ORNBQBCIOKFOEO-QGVNFLHTSA-N

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

HIDE SMILES / InChI

Molecular Formula	C21H32O2
Molecular Weight	316.4776
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	7 / 7
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24084011https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C82315
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18068870 | https://www.ncbi.nlm.nih.gov/pubmed/24385629 | https://www.ncbi.nlm.nih.gov/pubmed/21756978

Pregnenolone is an endogenous steroid and precursor the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineralocorticoids. In addition, pregnenolone is a precursor of neurosteroid pregnenolone sulfate, which is positive modulator of NMDA receptors and negative modulator of GABAA. Pregnenolone itself is a negative allosteric modulator of cannabinoid receptors. Pregnenolone is available as a dietary supplement, and is being investigated in clinical trials agains schizophrenia, bipolar disorder, major depressive disorder, marijuana dependency and other conditions.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
GABA-A receptor; anion channel 202 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24084011	Negative Allosteric Modulator 42	7.2 µM [IC50]
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1654510	Positive Allosteric Modulator 179	33.0 µM [EC50]
Transient receptor potential cation channel subfamily M member 1 3 Target ID: Q7Z4N2\|\|\|Q7Z4N3 Gene ID: 4308.0 Gene Symbol: TRPM1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/24084011	Activator 1430
Transient receptor potential cation channel subfamily M member 3 5 Target ID: Q9HCF6\|\|\|Q86SH6\|\|\|Q86Z01 Gene ID: 80036.0 Gene Symbol: TRPM3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/24084011	Activator 1430
Cannabinoid CB1 receptor 85 Target ID: CHEMBL218 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24385629	Negative Allosteric Modulator 42

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25781227	Primary	Preclinical	Unknown Approved Use Unknown
Spatial memory disorder 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10661509	Primary	Preclinical	Unknown Approved Use Unknown
Autism 19 Sources: https://clinicaltrials.gov/ct2/show/NCT01881737	Primary	Phase II 1132	PREGNENOLONE Approved Use Pregnenolone is a dietary supplement designed to promote mood and mental balance between body systems. Pregnenolone is a hormone similar to DHEA (dehydroepiandrosterone) and may be taken in addition to DHEA, or as an alternative. Pregnenolone is manufactured by many body tissues and under certain conditions, may be converted into similar substances, such as DHEA or progesterone.
Schizophrenia 298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21756978	Primary	Phase IV 63	PREGNENOLONE Approved Use Pregnenolone is a dietary supplement designed to promote mood and mental balance between body systems. Pregnenolone is a hormone similar to DHEA (dehydroepiandrosterone) and may be taken in addition to DHEA, or as an alternative. Pregnenolone is manufactured by many body tissues and under certain conditions, may be converted into similar substances, such as DHEA or progesterone.
Bipolar disorder 34 Sources: https://clinicaltrials.gov/ct2/show/NCT00223197	Primary	Phase IV 63	PREGNENOLONE Approved Use Pregnenolone is a dietary supplement designed to promote mood and mental balance between body systems. Pregnenolone is a hormone similar to DHEA (dehydroepiandrosterone) and may be taken in addition to DHEA, or as an alternative. Pregnenolone is manufactured by many body tissues and under certain conditions, may be converted into similar substances, such as DHEA or progesterone.
Major depressive disorder 173 Sources: https://clinicaltrials.gov/ct2/show/NCT00223197	Primary	Phase IV 63	PREGNENOLONE Approved Use Pregnenolone is a dietary supplement designed to promote mood and mental balance between body systems. Pregnenolone is a hormone similar to DHEA (dehydroepiandrosterone) and may be taken in addition to DHEA, or as an alternative. Pregnenolone is manufactured by many body tissues and under certain conditions, may be converted into similar substances, such as DHEA or progesterone.
Obsessive-compulsive disorder 28 Sources: https://clinicaltrials.gov/ct2/show/NCT01949753	Primary	Phase II 1132	PREGNENOLONE Approved Use Pregnenolone is a dietary supplement designed to promote mood and mental balance between body systems. Pregnenolone is a hormone similar to DHEA (dehydroepiandrosterone) and may be taken in addition to DHEA, or as an alternative. Pregnenolone is manufactured by many body tissues and under certain conditions, may be converted into similar substances, such as DHEA or progesterone.
Marijuana dependence 5 Sources: https://clinicaltrials.gov/ct2/show/NCT02439814	Primary	Phase II 1132	PREGNENOLONE Approved Use Pregnenolone is a dietary supplement designed to promote mood and mental balance between body systems. Pregnenolone is a hormone similar to DHEA (dehydroepiandrosterone) and may be taken in addition to DHEA, or as an alternative. Pregnenolone is manufactured by many body tissues and under certain conditions, may be converted into similar substances, such as DHEA or progesterone.

C_max

Value	Dose	Co-administered	Analyte	Population
38 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/15269827	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOPIDOGREL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
125.5 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/15269827	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOPIDOGREL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/15269827	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOPIDOGREL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
250 mg 2 times / day multiple, oral Highest studied dose Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24849255	unhealthy, 22.5 years (range: 18.1–35.5 years) n = 12 Health Status: unhealthy Condition: Autism Spectrum Disorder Age Group: 22.5 years (range: 18.1–35.5 years) Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/24849255	Sources: https://pubmed.ncbi.nlm.nih.gov/24849255

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:16581	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:16581
ChemicalBook	CB1684326	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1684326
MolPort	MolPort-002-506-906	https://www.molport.com/shop/molecule-link/MolPort-002-506-906
Selleck Chemicals	pregnenolone	http://www.selleckchem.com/products/pregnenolone.html
ZINC	ZINC000003861150	http://zinc15.docking.org/substances/ZINC000003861150
eMolecules	531097	https://www.emolecules.com/cgi-bin/more?vid=531097

PubMed

Title	Date	PubMed
Pregnenolone sulfate increases hippocampal acetylcholine release and spatial recognition.	2000 Jan 3	10661509
Neurosteroid analysis.	2001	11599313
Neurosteroid 7-hydroxylation products in the brain.	2001	11599312
Role of the peripheral-type benzodiazepine receptor in adrenal and brain steroidogenesis.	2001	11599298
Neurosteroids: beginning of the story.	2001	11599297
Effect of treatment of hypothyroidism on the plasma concentrations of neuroactive steroids and homocysteine.	2001 Aug	11592446
Effects of different steroid-biosynthesis inhibitors on the testicular steroidogenesis of the toad Bufo arenarum.	2001 Aug	11585264
Development of an enzyme immunoassay for serum 16-dehydropregnenolone.	2001 Aug	11510475
Neuroactive ring A-reduced metabolites of progesterone in human plasma during pregnancy: elevated levels of 5 alpha-dihydroprogesterone in depressed patients during the latter half of pregnancy.	2001 Dec	11739473
Differential involvement of the sigma(1) (sigma(1)) receptor in the anti-amnesic effect of neuroactive steroids, as demonstrated using an in vivo antisense strategy in the mouse.	2001 Dec	11739250
Identification, localization, and function in steroidogenesis of PAP7: a peripheral-type benzodiazepine receptor- and PKA (RIalpha)-associated protein.	2001 Dec	11731621
Adrenodoxin-cytochrome P450scc interaction as revealed by EPR spectroscopy: comparison with the putidaredoxin-cytochrome P450cam system.	2001 Dec	11726279
Implications of progesterone metabolism in MA-10 cells for accurate measurement of the rate of steroidogenesis.	2001 Dec	11713220
Diminished allopregnanolone enhancement of GABA(A) receptor currents in a rat model of chronic temporal lobe epilepsy.	2001 Dec 1	11731578
Adenosine A2A, 5-HT1A and 5-HT7 receptor in neonatally pregnenolone-treated rats.	2001 Dec 4	11726792
Cerebral venous thrombosis in a patient of paroxysmal nocturnal haemoglobinuria following aplastic anaemia.	2001 Jul	11573565
Ontogeny of steroid metabolizing enzymes in rat oligodendrocytes.	2001 Jul	11530289
Serum concentration of androstenediol and androstenediol sulfate in patients with hyperthyroidism and hypothyroidism.	2001 Jun	11523906
Luteinization factor-stimulated steroidogenesis in porcine granulosa cells.	2001 Jun	11519688
Neurosteroids: recent findings.	2001 Nov	11744081
The interaction between neuroactive steroids and the sigma1 receptor function: behavioral consequences and therapeutic opportunities.	2001 Nov	11744080
Anatomical and biochemical evidence for the synthesis of unconjugated and sulfated neurosteroids in amphibians.	2001 Nov	11744071
Influence of membrane cholesterol on modulation of the GABA(A) receptor by neuroactive steroids and other potentiators.	2001 Nov	11704651
Immunoelectron microscopic localization of three key steroidogenic enzymes (cytochrome P450(scc), 3 beta-hydroxysteroid dehydrogenase and cytochrome P450(c17)) in rat adrenal cortex and gonads.	2001 Nov	11691658
Influence of neurosteroids on the development of rapid tolerance to ethanol in mice.	2001 Nov 16	11728424
Hormonal steroidogenesis in liver and small intestine of the green frog, Rana esculenta L.	2001 Nov 2	11720095
Neuroactive steroids modulate crustacean locomotor activity.	2001 Nov 2	11684341
Identification of ST2A1 as a rat brain neurosteroid sulfotransferase mRNA.	2001 Nov 30	11716829
Automated chromatographic system for the simultaneous measurement of plasma pregnenolone and 17-hydroxypregnenolone by radioimmunoassay.	2001 Nov 5	11710589
Increased testicular steroid concentrations in patients with idiopathic infertility and normal FSH levels.	2001 Nov-Dec	11695840
Acute effects of ethanol on steroidogenic acute regulatory protein (StAR) in the prepubertal rat ovary.	2001 Oct	11696671
Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes.	2001 Oct	11695850
Opposite effects of short- versus long-term administration of fluoxetine on the concentrations of neuroactive steroids in rat plasma and brain.	2001 Oct	11685383
Prevention of the stress-induced increase in frontal cortical dopamine efflux of freely moving rats by long-term treatment with antidepressant drugs.	2001 Oct	11597820
Aldosterone increases T-type calcium currents in human adrenocarcinoma (H295R) cells by inducing channel expression.	2001 Oct	11564691
2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands.	2001 Oct	11557354
Activity and localization of 3beta-hydroxysteroid dehydrogenase/ Delta5-Delta4-isomerase in the zebrafish central nervous system.	2001 Oct 22	11596055
Purification of cytochromes P-450(scc) and P-450(17 alpha) by steroid-binding affinity column chromatography.	2001 Oct 30	11694291
Immunohistochemical localization of steroidogenic enzymes in the corpus luteum and the placenta of the ribbon seal (Phoca fasciata) and steller sea lion (Eumetopias jubatus).	2001 Sep	11642282
Analysis of neurosteroid levels in attention deficit hyperactivity disorder.	2001 Sep	11602031
Pregnenolone sulfate and aging of cognitive functions: behavioral, neurochemical, and morphological investigations.	2001 Sep	11534985
Subunit-specific modulation of glycine receptors by neurosteroids.	2001 Sep	11522328
Cytochrome P450 in the brain; a review.	2001 Sep	11513329
Regulation of the rat glutathione S-transferase A2 gene by glucocorticoids: involvement of both the glucocorticoid and pregnane X receptors.	2001 Sep	11502894
Pregnenolone sulfate modulates angiotensin II-induced inositol 1,4,5-trisphosphate changes in the anterior pituitary of female rat.	2001 Sep 28	11563852
Membrane cholesterol modulates serotonin transporter activity.	2001 Sep 4	11523992
Neuroactive steroid levels in patients with generalized anxiety disorder.	2001 Summer	11514647
Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor.	2002 Jan 25	11706036
Pregnenolone sulfate: from steroid metabolite to TRP channel ligand.	2013 Sep 27	24084011
Pregnenolone sulfate normalizes schizophrenia-like behaviors in dopamine transporter knockout mice through the AKT/GSK3β pathway.	2015 Mar 17	25781227

Patents

Sample Use Guides

In Vivo Use Guide

In the model of schizophrenia, pregnenolone sulfate was administered to mice intraperitoneally at 40 or 60 mg/kg. When administered to rats intracerebroventricularly, 12 nmol but not 192 nmol pregnenolone sulfate enhanced spatial memory performance.

Route of Administration: Other

In Vitro Use Guide

Activity with respect to NMDA and GABA uiion channels was measured using whole cell variant of the patch-clamp technique. Patch electrodes were fabricated with a double pull from thin-wall borosilicate glass microcapillary pipets. Electrode resistance was 5.2 ± 0.12 MOhm (n = 65) when filled with intracellular solution. After formation of a tight seal (typically 1-10 GOhm), capacitative transients were minimized. The patch of membrane under the pipet tip was then ruptured by gentle suction, to obtain the whole-cell configuration. Drug solutions were applied to single neurons by pressure ejection (15 psi) from seven-barrel pipets. Under these conditions, the drug solution in the pressure pipet rapidly and effectively replaces the solution surrounding the target neuron, with <10% dilution. In all experiments, neurons received a 10-sec prepulse of either external buffer or drug solution, followed by a 10-sec application of agonist, followed by a 10-20-sec pulse of external buffer solution.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:13:51 GMT 2023` Edited by `admin` on `Sat Dec 16 17:13:51 GMT 2023`
Record UNII	73R90F7MQ8
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

Pregnenolone

Official Name

English

17.BETA.-(1-KETOETHYL)-.DELTA. SUP(5)-ANDROSTEN-3.BETA.-OL

Common Name

English

NSC-18158

Code

English

.DELTA. SUP(5)-PREGNEN-3.BETA.-OL-20-ONE

Common Name

English

PREGN-5-EN-20-ONE, 3-(3-CARBOXY-, (3.BETA.)-

Common Name

English

PREGNENOLONE [JAN]

Common Name

English

PREGNENOLONE [VANDF]

Common Name

English

NSC-1616

Code

English

ARTHENOLONE

Common Name

English

ENELONE

Common Name

English

PREGNENOLONE [MI]

Common Name

English

Pregnenolone [WHO-DD]

Common Name

English

pregnenolone [INN]

Common Name

English

3.BETA.-HYDROXYPREGN-5-EN-20-ONE

Systematic Name

English

Classification Tree Code System Code

LOINC

13894-1