Medication and supplement
This article is about pregnenolone as a medication and supplement. For its role as a hormone, see
Pregnenolone .
Pregnenolone
Trade names Arthenolone, Bina-Skin, Enelone, Natolone, Pregneton, Prenolone, Regnosone, Sharmone, Skinostelon
[1]
[2] Other names P5; 5-Pregnenolone; δ5 -Pregnene-3β-ol-20-one; Pregn-5-en-3β-ol-20-one; NSC-1616
AHFS /
Drugs.com
International Drug Names
Routes of administration
By mouth ,
transdermal
Drug class
Neurosteroid ;
Anti-inflammatory
ATC code
Legal status
1-[(3S ,8S ,9S ,10R ,13S ,14S ,17S )-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H -cyclopenta[a ]phenanthren-17-yl]ethanone
CAS Number
PubChem
CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Formula C 21 H 32 O 2
Molar mass 316.485 g·mol−1 3D model (
JSmol )
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=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
Y Key:ORNBQBCIOKFOEO-QGVNFLHTSA-N
Y
(verify)
Pregnenolone , sold under the brand name Enelone among others, is a
medication and
supplement as well as a
naturally occurring and
endogenous
steroid .
[3]
[1]
[4]
[5]
[6] It is described as a
neurosteroid and
anti-inflammatory drug and was used in the treatment of
rheumatoid arthritis and
soft-tissue
rheumatism in the 1950s but is no longer used today.
[3]
[2]
[4] Pregnenolone can be taken
by mouth , as a
topical medication , or by
injection into muscle .
[3]
[2]
Pregnenolone is promoted online with false claims that it can treat a variety of health conditions including
cancer ,
arthritis and
multiple sclerosis .
[7]
Medical uses
Pregnenolone was approved for use as a
pharmaceutical medication in the treatment of
rheumatoid arthritis and
soft-tissue
rheumatism in the 1950s.
[2] It is no longer used today.
[4]
Available forms
Pregnenolone acetate was available as Enelone in the form of 100 mg
oral
tablets and as a 100 mg/mL
crystalline
aqueous suspension in 10 mL
vials .
[2]
Pharmacology
Pregnenolone is a
neurosteroid .
[5]
[6] It is a
negative allosteric modulator of the
CB1 receptor ,
[5]
[8] a
ligand of the
microtubule-associated protein 2 (MAP2),
[9]
[10] and an
agonist of the
pregnane X receptor .
[11] Pregnenolone has no
progestogenic ,
corticosteroid ,
estrogenic ,
androgenic , or
antiandrogenic activity.
[3] In addition to its own activities, pregnenolone is a
precursor for other neurosteroids such as
pregnenolone sulfate ,
allopregnanolone , and
pregnanolone and for
steroid hormones .
[12]
[13]
[14]
[15]
Pregnenolone has low
bioavailability and is subject to high
metabolism .
[5]
Oral administration of 50 or 100 mg pregnenolone has been found to have minimal or negligible effect on
urinary levels of
testosterone and testosterone
metabolites , including of
androsterone ,
etiocholanolone ,
5β-androstanediol ,
androstadienol , and
androstenol (and/or their
conjugates ), and this suggests that only a small amount of pregnenolone is converted into testosterone.
[13]
[14] This is in accordance with findings on the conversion of
DHEA into testosterone, in which only 1.5% of an oral dose of DHEA was found to be converted into testosterone.
[13] In contrast to the
androstanes , 50 or 100 mg oral pregnenolone has been found to significantly and in fact "strongly" increase urinary levels of the progesterone metabolites
pregnanediol and
pregnanolone (and/or their conjugates), whereas
pregnanetriol was unaffected.
[13]
[14] Unlike the case of oral administration,
transdermal administration of 30 mg/day pregnenolone cream has not been found to affect urinary levels of metabolites of any other steroids, including of progesterone.
[14]
Intranasal administration of pregnenolone was found to have low bioavailability of around 23%.
[5]
Sripada et al. reported that oral pregnenolone is preferentially metabolized into the
neurosteroid
allopregnanolone rather than into other steroids such as DHEA or
cortisol .
[15] In further research by their group, a single 400 mg dose of oral pregnenolone at 3 hours post-administration was found to result in a 3-fold elevation in serum levels of pregnenolone and a 7-fold increase in allopregnanolone levels.
[15] Pregnanolone levels increased by approximately 60% while DHEA levels decreased non-significantly by approximately 5% and cortisol levels were not affected.
[15] Another study found that allopregnanolone levels were increased by 3-fold at 2 hours post-administration following a single 400 mg oral dose of pregnenolone.
[15]
In addition to allopregnanolone, pregnenolone acts as a
prodrug of pregnenolone sulfate.
[12] However, pregnenolone sulfate does not cross the
blood–brain barrier .
[16]
[17]
Chemistry
Pregnenolone, also known as 5-pregnenolone or as pregn-5-en-3β-ol-20-one, is a
naturally occurring
pregnane
steroid and a
derivative of
cholesterol .
[3]
[1]
[4] Related steroids include
pregnenolone sulfate ,
3β-dihydroprogesterone (4-pregnenolone),
progesterone ,
allopregnanolone , and
pregnanolone .
[3]
[1]
[4]
Derivatives
A few
synthetic
ester
derivatives of pregnenolone exist.
[1] These include
pregnenolone acetate (Antofin, Previsone, Pregno-Pan) and
pregnenolone succinate (Panzalone, Formula 405).
[1]
Prebediolone acetate (Acetoxanon, Acetoxy-Prenolon, Artisone, Artivis, Pregnartrone, Sterosone), the 21-
acetate
ester of
21-hydroxypregnenolone , also exists.
[1] These esters are all described as
glucocorticoids similarly to pregnenolone.
[1]
The 3β-
methyl
ether of pregnenolone,
3β-methoxypregnenolone (MAP-4343), retains similar activity to pregnenolone in regard to interaction with MAP2,
[9]
[10] and is under development for potential clinical use for indications such as the treatment of
brain and
spinal cord injury and
depressive disorders .
[18]
[19]
[20]
[21]
History
Pregnenolone was first
synthesized by
Adolf Butenandt and colleagues in 1934.
[3] It was first used in medicine, as an
anti-inflammatory medication, in the 1940s.
[5]
Society and culture
Generic names
Pregnenolone is the
generic name of the drug and its
INN Tooltip International Nonproprietary Name ,
BAN Tooltip British Approved Name ,
DCF Tooltip Dénomination Commune Française , and
JAN Tooltip Japanese Accepted Name .
[1]
[4]
[22]
Brand names
Pregnenolone has been marketed in the past under a variety of brand names including Arthenolone, Bina-Skin, Enelone, Natolone, Pregnetan, Pregneton, Pregnolon, Prenolon, Prenolone, Regnosone, Sharmone, and Skinostelon.
[1]
[4]
Availability
Pregnenolone is no longer marketed as a medication, but remains available as a supplement.
[4]
[23]
Alternative medicine
Pregnenolone has been promoted online with claims it can treat a variety of diseases including
multiple sclerosis ,
arthritis , and
cancer , but such claims are not backed by evidence.
[7]
Research
As of 2016
[update] pregnenolone is being researched for possible therapeutic applications, but its poor
bioavailability makes its prospects for usefulness low.
[5] Pregnenolone is available as an
over-the-counter
supplement , for instance in the
United States .
[23]
See also
References
^
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f
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i
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^ Pertwee RG (2015). "Endocannabinoids and Their Pharmacological Actions". Endocannabinoids . Handbook of Experimental Pharmacology. Vol. 231. Springer International Publishing. pp. 1–37.
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ISBN
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"Neurosteroid regulation of central nervous system development" . Pharmacology & Therapeutics . 116 (1): 107–124.
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PMC
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^
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"Microtubule-associated protein 2 (MAP2) is a neurosteroid receptor" . Proceedings of the National Academy of Sciences of the United States of America . 103 (12): 4711–4716.
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PMID
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^
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b Ducharme N, Banks WA, Morley JE, Robinson SM, Niehoff ML, Mattern C, Farr SA (September 2010).
"Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration" . European Journal of Pharmacology . 641 (2–3): 128–134.
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^
a
b
c
d Saudan C, Desmarchelier A, Sottas PE, Mangin P, Saugy M (March 2005). "Urinary marker of oral pregnenolone administration". Steroids . 70 (3): 179–183.
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^
a
b
c
d Piper T, Schlug C, Mareck U, Schänzer W (May 2011). "Investigations on changes in ¹³C/¹²C ratios of endogenous urinary steroids after pregnenolone administration". Drug Testing and Analysis . 3 (5): 283–290.
doi :
10.1002/dta.281 .
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^
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b
c
d
e Sripada RK, Marx CE, King AP, Rampton JC, Ho SS, Liberzon I (June 2013).
"Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits" . Biological Psychiatry . 73 (11): 1045–1053.
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^ Klein P, Janousek J (18 June 2010).
"Impact of Neuroendocrine Factors on Seizure Genesis and Treatment" . In Rho J, Sankar R, Stafstrom CE (eds.). Epilepsy: Mechanisms, Models, and Translational Perspectives . CRC Press. pp. 479–.
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^ CIBA Foundation Symposium (30 April 2008).
Steroids and Neuronal Activity . John Wiley & Sons. pp. 101–.
ISBN
978-0-470-51399-6 .
^
"Pregnenolone methyl ether" . AdisInsight . Springer Nature Switzerland AG.
^ Duchossoy Y, David S, Baulieu EE, Robel P (July 2011). "Treatment of experimental spinal cord injury with 3β-methoxy-pregnenolone". Brain Research . 1403 : 57–66.
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10.1016/j.brainres.2011.05.065 .
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^ Bianchi M, Baulieu EE (January 2012).
"3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders" . Proceedings of the National Academy of Sciences of the United States of America . 109 (5): 1713–1718.
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^ Baulieu ÉÉ (2015).
"From steroid hormones to depressive states and senile dementias: New mechanistic, therapeutical and predictive approaches" . Comptes Rendus Biologies . 338 (8–9): 613–616.
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^
"145-13-1 - ORNBQBCIOKFOEO-QGVNFLHTSA-N - Pregnenolone [INN:BAN] - Similar structures search, synonyms, formulas, resource links, and other chemical information" . ChemIDplus . U.S. National Library of Medicine.
^
a
b Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM (May 2004). "Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation". Psychoneuroendocrinology . 29 (4): 486–500.
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36847870 .
Receptor (
ligands )
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Agonists
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A-796,260
A-834,735
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AZ-11713908
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PF-03550096
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UR-144
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Receptor (
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D12-116
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Negative modulators:
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