PREGNENOLONE SULFATE

US Previously Marketed

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

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

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
Neurosteroid 7-hydroxylation products in the brain.	2001	11599312
Oxidized adrenodoxin acts as a competitive inhibitor of cytochrome P450scc in mitochondria from the human placenta.	2001 Apr	11298752
cyp7b1 catalyses the 7alpha-hydroxylation of dehydroepiandrosterone and 25-hydroxycholesterol in rat prostate.	2001 Apr 15	11284740
Tracking the role of a star in the sky of the new millennium.	2001 Aug	11463850
Neurosteroid synthesis by cytochrome p450-containing systems localized in the rat brain hippocampal neurons: N-methyl-D-aspartate and calcium-dependent synthesis.	2001 Aug	11459806
Decreased expression of steroidogenic acute regulatory protein: a novel mechanism participating in the leptin-induced inhibition of glucocorticoid biosynthesis.	2001 Aug	11459771
Adrenodoxin-cytochrome P450scc interaction as revealed by EPR spectroscopy: comparison with the putidaredoxin-cytochrome P450cam system.	2001 Dec	11726279
Adenosine A2A, 5-HT1A and 5-HT7 receptor in neonatally pregnenolone-treated rats.	2001 Dec 4	11726792
Steroids differentially inhibit the nicotinic acetylcholine receptor.	2001 Feb 12	11209925
The expression of pregnane X receptor and its target gene, cytochrome P450 3A1, in perinatal mouse.	2001 Feb 14	11165039
The octadecaneuropeptide ODN stimulates neurosteroid biosynthesis through activation of central-type benzodiazepine receptors.	2001 Jan	11145985
Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor.	2001 Jan	11145608
Assessment of mechanisms of thyroid hormone action in mouse Leydig cells: regulation of the steroidogenic acute regulatory protein, steroidogenesis, and luteinizing hormone receptor function.	2001 Jan	11145595
Bacterially produced apolipoprotein D binds progesterone and arachidonic acid, but not bilirubin or E-3M2H.	2001 Jan-Feb	11180564
Ontogeny of steroid metabolizing enzymes in rat oligodendrocytes.	2001 Jul	11530289
Neuroactive steroid-serotonergic interaction: responses to an intravenous L-tryptophan challenge in women with premenstrual syndrome.	2001 Jul	11415849
Luteinization factor-stimulated steroidogenesis in porcine granulosa cells.	2001 Jun	11519688
Molecular modelling of 17 alpha-hydroxylase-17,20-lyase.	2001 Jun	11446160
Troglitazone is a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase enzyme in the ovary.	2001 Mar	11262455
Enhanced dehydroepiandrosterone synthesis by amnion compared to chorion: a comparative study using the reverse-isotope dilution technique.	2001 Mar	11170268
[Effect of genotype and social stress on cAMP- and substrate-dependent mechanisms of regulating hormonal function of testis in mice].	2001 May	11436557
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
Identification of ST2A1 as a rat brain neurosteroid sulfotransferase mRNA.	2001 Nov 30	11716829
Increased testicular steroid concentrations in patients with idiopathic infertility and normal FSH levels.	2001 Nov-Dec	11695840
2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands.	2001 Oct	11557354
Pregnenolone sulfate and aging of cognitive functions: behavioral, neurochemical, and morphological investigations.	2001 Sep	11534985
Cytochrome P450 in the brain; a review.	2001 Sep	11513329
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.

Name

Type

Language

PREGNENOLONE SULFATE

Common Name

English

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

Systematic Name

English

Code System Code Type Description

MESH

C018370