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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 |
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Chemical and physical data | |
Formula | C21H32O2 |
Molar mass | 316.485 g·mol−1 |
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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 and is no longer prescribed today, but remains available as a supplement. [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]
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]
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]
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]
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]
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]
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]
Pregnenolone is the generic name of the drug and its INN , BAN , DCF , and JAN . [1] [4] [22]
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]
Pregnenolone is no longer marketed as a medication, but remains available as a supplement. [4] [23]
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]
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]