Pregnenolone (medication)
Medication and supplement From Wikipedia, the free encyclopedia
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]
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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 |
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| Routes of administration | By mouth, transdermal |
| Drug class | Neurosteroid; Anti-inflammatory |
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| Formula | C21H32O2 |
| Molar mass | 316.485 g·mol−1 |
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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
Summarize
Perspective
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, BAN, DCF, and JAN.[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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