PREGNENOLONE SULFATE

First approved in 1950

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H32O5S
Molecular Weight	396.541
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@H](CC[C@]4(C)[C@H]3CC[C@]12C)OS(O)(=O)=O

InChI

InChIKey=DIJBBUIOWGGQOP-QGVNFLHTSA-N

InChI=1S/C21H32O5S/c1-13(22)17-6-7-18-16-5-4-14-12-15(26-27(23,24)25)8-10-20(14,2)19(16)9-11-21(17,18)3/h4,15-19H,5-12H2,1-3H3,(H,23,24,25)/t15-,16-,17+,18-,19-,20-,21+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C21H32O5S
Molecular Weight	396.541
Charge	0
Count

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

Description
Sources: https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C82315https://www.ncbi.nlm.nih.gov/pubmed/24084011
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25781227 https://www.ncbi.nlm.nih.gov/pubmed/10661509

Pregnenolone sulfate is an endogenous neurosteroid with excitatory effects in the brain, acting as a potent negative allosteric modulator of the GABAA receptor, a positive allosteric modulator of the NMDA receptor, and activator of transient receptor potential cation channel TRPM1 and TRPM3. In the model of schizophrenia, treatment with pregnenolone sulfate normalized the hyperlocomotion and stereotypic bouts, and rescued the PPI deficits of dopamine transporter knockout mice. Promnesic properties of pregnenolone sulfate were demonstrated in rat models of spatial memory performance.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
GABA-A receptor; anion channel 203 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24084011	Negative Allosteric Modulator 43	7.2 µM [IC50]
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1654510	Positive Allosteric Modulator 186	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 1447
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 1447
Cannabinoid CB1 receptor 85 Target ID: CHEMBL218 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24385629	Negative Allosteric Modulator 43

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 305 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 20 Sources: https://clinicaltrials.gov/ct2/show/NCT01881737	Primary	Phase II 1147	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 305 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 179 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 33 Sources: https://clinicaltrials.gov/ct2/show/NCT01949753	Primary	Phase II 1147	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 1147	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

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
eMolecules	531097	https://www.emolecules.com/cgi-bin/more?vid=531097
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

PubMed

Title	Date	PubMed
Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor.	2002-01-25	11706036
Adenosine A2A, 5-HT1A and 5-HT7 receptor in neonatally pregnenolone-treated rats.	2001-12-04	11726792
Diminished allopregnanolone enhancement of GABA(A) receptor currents in a rat model of chronic temporal lobe epilepsy.	2001-12-01	11731578
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.	2001-12	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.	2001-12	11739250
Identification, localization, and function in steroidogenesis of PAP7: a peripheral-type benzodiazepine receptor- and PKA (RIalpha)-associated protein.	2001-12	11731621
Adrenodoxin-cytochrome P450scc interaction as revealed by EPR spectroscopy: comparison with the putidaredoxin-cytochrome P450cam system.	2001-12	11726279
Implications of progesterone metabolism in MA-10 cells for accurate measurement of the rate of steroidogenesis.	2001-12	11713220
Identification of ST2A1 as a rat brain neurosteroid sulfotransferase mRNA.	2001-11-30	11716829
Influence of neurosteroids on the development of rapid tolerance to ethanol in mice.	2001-11-16	11728424
Increased testicular steroid concentrations in patients with idiopathic infertility and normal FSH levels.	2001-11-07	11695840
Automated chromatographic system for the simultaneous measurement of plasma pregnenolone and 17-hydroxypregnenolone by radioimmunoassay.	2001-11-05	11710589
Hormonal steroidogenesis in liver and small intestine of the green frog, Rana esculenta L.	2001-11-02	11720095
Neuroactive steroids modulate crustacean locomotor activity.	2001-11-02	11684341
Neurosteroids: recent findings.	2001-11	11744081
The interaction between neuroactive steroids and the sigma1 receptor function: behavioral consequences and therapeutic opportunities.	2001-11	11744080
Anatomical and biochemical evidence for the synthesis of unconjugated and sulfated neurosteroids in amphibians.	2001-11	11744071
Influence of membrane cholesterol on modulation of the GABA(A) receptor by neuroactive steroids and other potentiators.	2001-11	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.	2001-11	11691658
Purification of cytochromes P-450(scc) and P-450(17 alpha) by steroid-binding affinity column chromatography.	2001-10-30	11694291
Activity and localization of 3beta-hydroxysteroid dehydrogenase/ Delta5-Delta4-isomerase in the zebrafish central nervous system.	2001-10-22	11596055
Acute effects of ethanol on steroidogenic acute regulatory protein (StAR) in the prepubertal rat ovary.	2001-10	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.	2001-10	11695850
Opposite effects of short- versus long-term administration of fluoxetine on the concentrations of neuroactive steroids in rat plasma and brain.	2001-10	11685383
Prevention of the stress-induced increase in frontal cortical dopamine efflux of freely moving rats by long-term treatment with antidepressant drugs.	2001-10	11597820
Aldosterone increases T-type calcium currents in human adrenocarcinoma (H295R) cells by inducing channel expression.	2001-10	11564691
2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands.	2001-10	11557354
Pregnenolone sulfate modulates angiotensin II-induced inositol 1,4,5-trisphosphate changes in the anterior pituitary of female rat.	2001-09-28	11563852
Membrane cholesterol modulates serotonin transporter activity.	2001-09-04	11523992
Immunohistochemical localization of steroidogenic enzymes in the corpus luteum and the placenta of the ribbon seal (Phoca fasciata) and steller sea lion (Eumetopias jubatus).	2001-09	11642282
Analysis of neurosteroid levels in attention deficit hyperactivity disorder.	2001-09	11602031
Pregnenolone sulfate and aging of cognitive functions: behavioral, neurochemical, and morphological investigations.	2001-09	11534985
Subunit-specific modulation of glycine receptors by neurosteroids.	2001-09	11522328
Cytochrome P450 in the brain; a review.	2001-09	11513329
Regulation of the rat glutathione S-transferase A2 gene by glucocorticoids: involvement of both the glucocorticoid and pregnane X receptors.	2001-09	11502894
Stimulatory effect of lactate on testosterone production by rat Leydig cells.	2001-08-14	11500963
Effect of treatment of hypothyroidism on the plasma concentrations of neuroactive steroids and homocysteine.	2001-08	11592446
Effects of different steroid-biosynthesis inhibitors on the testicular steroidogenesis of the toad Bufo arenarum.	2001-08	11585264
Development of an enzyme immunoassay for serum 16-dehydropregnenolone.	2001-08	11510475
Heterozygous mutation in the cholesterol side chain cleavage enzyme (p450scc) gene in a patient with 46,XY sex reversal and adrenal insufficiency.	2001-08	11502818
Cerebral venous thrombosis in a patient of paroxysmal nocturnal haemoglobinuria following aplastic anaemia.	2001-07	11573565
Ontogeny of steroid metabolizing enzymes in rat oligodendrocytes.	2001-07	11530289
Serum concentration of androstenediol and androstenediol sulfate in patients with hyperthyroidism and hypothyroidism.	2001-06	11523906
Luteinization factor-stimulated steroidogenesis in porcine granulosa cells.	2001-06	11519688
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
Neuroactive steroid levels in patients with generalized anxiety disorder.	2001	11514647
[Neurosteroids, their role in brain physiology: neurotrophicity, memory, aging...].	2001	11474590

Patents

Sample Use Guides

In Vivo Use Guide

Pregnenolone supplements are administered orally at 100-500 mg a day.

Route of Administration: Oral

In Vitro Use Guide

Pregnenolone (between 10nMand 1 μM, depending on the cellular model) inhibited the increase in P-Erk1/2MAPK and the decrease in cellular and mitochondrial respiration induced by tetrahydrocannabinol in cells transfected with human CB1 receptor.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:59:59 GMT 2025` Edited by `admin` on `Mon Mar 31 22:59:59 GMT 2025`
Record UNII	04Y4D91RG0
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

PREGNENOLONE SULFATE

Common Name

English

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

Preferred Name

English

Code System Code Type Description

MESH

C018370