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

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://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 7-hydroxylation products in the brain.	2001	11599312
Neurosteroids: beginning of the story.	2001	11599297
[Neurosteroids, their role in brain physiology: neurotrophicity, memory, aging...].	2001	11474590
Mechanism of action of noradrenaline on secretion of progesterone and oxytocin by the bovine corpus luteum in vitro.	2001	11402689
Effects of hyperprolactinemia on testosterone production in rat Leydig cells.	2001	11135360
Direct inhibitory effect of digitalis on progesterone release from rat granulosa cells.	2001 Apr	11309248
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
Heterozygous mutation in the cholesterol side chain cleavage enzyme (p450scc) gene in a patient with 46,XY sex reversal and adrenal insufficiency.	2001 Aug	11502818
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
Diminished allopregnanolone enhancement of GABA(A) receptor currents in a rat model of chronic temporal lobe epilepsy.	2001 Dec 1	11731578
A high dose of vitamin E inhibits adrenal corticosterone synthesis in chickens treated with ACTH.	2001 Feb	11349889
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
Androgens and aging.	2001 Feb 28	11311591
Pregnenolone protects mouse hippocampal (HT-22) cells against glutamate and amyloid beta protein toxicity.	2001 Jan	11358277
The octadecaneuropeptide ODN stimulates neurosteroid biosynthesis through activation of central-type benzodiazepine receptors.	2001 Jan	11145985
Allopregnanolone, pregnenolone sulfate, and epitestosterone in breast cyst fluid.	2001 Jan	11090659
Bacterially produced apolipoprotein D binds progesterone and arachidonic acid, but not bilirubin or E-3M2H.	2001 Jan-Feb	11180564
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
Neuroactive steroid-serotonergic interaction: responses to an intravenous L-tryptophan challenge in women with premenstrual syndrome.	2001 Jul	11415849
Expression and characterization of the human 3 beta-hydroxysteroid sulfotransferases (SULT2B1a and SULT2B1b).	2001 Jun	11457664
Aryl hydrocarbon receptor (AhR)-linked inhibition of luteal cell progesterone secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin treated cells.	2001 Jun	11453109
Molecular modelling of 17 alpha-hydroxylase-17,20-lyase.	2001 Jun	11446160
Steroids in the nervous system: a Pandora's box?	2001 Jun	11421230
Creation and activity of COS-1 cells stably expressing the F2 fusion of the human cholesterol side-chain cleavage enzyme system.	2001 Jun	11356706
Leukemia inhibitory factor antagonizes gonadotropin induced-testosterone synthesis in cultured porcine leydig cells: sites of action.	2001 Jun	11356700
Troglitazone is a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase enzyme in the ovary.	2001 Mar	11262455
Progestins block cholesterol synthesis to produce meiosis-activating sterols.	2001 Mar	11259396
Enhanced dehydroepiandrosterone synthesis by amnion compared to chorion: a comparative study using the reverse-isotope dilution technique.	2001 Mar	11170268
Neurosteroid-induced enhancement of glutamate transmission in rat hippocampal slices.	2001 Mar 30	11248433
Repellent activity of estrogenic compounds toward zoospores of the phytopathogenic fungus Aphanomyces cochlioides.	2001 Mar-Apr	11371017
[Effect of genotype and social stress on cAMP- and substrate-dependent mechanisms of regulating hormonal function of testis in mice].	2001 May	11436557
Pregnane X receptor: molecular basis for species differences in CYP3A induction by xenobiotics.	2001 May 16	11336976
Neurosteroids: recent findings.	2001 Nov	11744081
The interaction between neuroactive steroids and the sigma1 receptor function: behavioral consequences and therapeutic opportunities.	2001 Nov	11744080
Influence of membrane cholesterol on modulation of the GABA(A) receptor by neuroactive steroids and other potentiators.	2001 Nov	11704651
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
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
Subunit-specific modulation of glycine receptors by neurosteroids.	2001 Sep	11522328
Neuroactive steroid levels in patients with generalized anxiety disorder.	2001 Summer	11514647
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 10:03:36 GMT 2023` Edited by `admin` on `Sat Dec 16 10:03:36 GMT 2023`
Record UNII	04Y4D91RG0
Record Status	`Validated (UNII)`
Record Version

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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