Pregnenolone, sold under the brand name Enelone among others, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

and

supplement Supplement or Supplemental may refer to: Health and medicine * Bodybuilding supplement * Dietary supplement * Herbal supplement Media * Supplement (publishing), a publication that has a role secondary to that of another preceding or concurrent ...

as well as a

naturally occurring A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical ...

and

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

. It is described as a

neurosteroid Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term ''neurosteroid'' was coi ...

and

anti-inflammatory drug Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechani ...

and was used in the treatment of

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

and

soft-tissue Soft tissue connects and surrounds or supports internal organs and bones, and includes muscle, tendons, ligaments, fat, fibrous tissue, lymph and blood vessels, fasciae, and synovial membranes. Soft tissue is tissue in the body that is not har ...

rheumatism Rheumatism or rheumatic disorders are conditions causing chronic, often intermittent pain affecting the joints or connective tissue. Rheumatism does not designate any specific disorder, but covers at least 200 different conditions, including a ...

in the 1950s and is no longer prescribed today, but remains available as a supplement. Pregnenolone can be taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

, as a

topical medication A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surface area, body surfaces such as the skin or mucous membranes to treat ailments via a large ...

, or by injection into muscle. Pregnenolone is promoted online with false claims that it can treat a variety of health conditions including

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

arthritis Arthritis is a general medical term used to describe a disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, Joint effusion, swelling, and decreased range of motion of ...

and

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

Medical uses

Pregnenolone was approved for use as a

pharmaceutical medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the m ...

in the treatment of

and

in the 1950s. It is no longer used today.

Available forms

Pregnenolone acetate Pregnenolone acetate (brand names Antofin, Previsone, Pregno-Pan), also known as pregn-5-en-3β-ol-20-one 3β-acetate, is a synthetic pregnane steroid and an ester of pregnenolone which is described as a glucocorticoid and as a skin-conditioning ...

was available as Enelone in the form of 100 mg

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

tablets and as a 100 mg/mL

crystalline A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macrosc ...

aqueous suspension In chemistry, a suspension is a heterogeneous mixture of a fluid that contains solid particles sufficiently large for sedimentation. The particles may be visible to the naked eye, usually must be larger than one micrometer, and will eventually s ...

in 10 mL

vial A vial (also known as a phial or flacon) is a small glass or plastic vessel or bottle, often used to store medication in the form of liquids, powders, or capsules. They can also be used as scientific sample vessels; for instance, in autosam ...

Pharmacology

Pregnenolone is a

. It is a

negative allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that a ...

of the CB₁ receptor, a

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

of the microtubule-associated protein 2 (MAP2), and an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the

pregnane X receptor In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the ' ...

. Pregnenolone has no

progestogen Progestogens, also sometimes written progestins, progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestoge ...

ic,

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

ic,

androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

ic, or

antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking t ...

ic activity. In addition to its own activities, pregnenolone is a

precursor Precursor or Precursors may refer to: *Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), hypothesized genus of fossil birds that was composed of fossilized parts of unre ...

for other neurosteroids such as

pregnenolone sulfate Pregnenolone sulfate (PS, PREGS) is an endogenous excitatory neurosteroid that is synthesized from pregnenolone. It is known to have cognitive and memory-enhancing, antidepressant, anxiogenic, and proconvulsant effects. Biological activi ...

allopregnanolone Allopregnanolone is a natural product, naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to t ...

, and

pregnanolone Pregnanolone, also known as eltanolone, is an endogenous inhibitory neurosteroid which is produced in the body from progesterone. It is closely related to allopregnanolone, which has similar properties. Biological activity Pregnanolone is a pos ...

and for

steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Wit ...

s. Pregnenolone has low

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

and is subject to high

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

Oral administration Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

of 50 or 100 mg pregnenolone has been found to have minimal or negligible effect on

urinary The human urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressu ...

levels of

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

and testosterone

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s, including of

androsterone Androsterone, or 3α-hydroxy-5α-androstan-17-one, is an endogenous steroid hormone, neurosteroid, and putative pheromone. It is a weak androgen with a potency that is approximately 1/7 that of testosterone. Androsterone is a metabolite of te ...

etiocholanolone Etiocholanolone, also known as 5β-androsterone, as well as 3α-hydroxy-5β-androstan-17-one or etiocholan-3α-ol-17-one, is an etiocholane (5β-androstane) steroid as well as an endogenous 17-ketosteroid that is produced from the metabolism o ...

5β-androstanediol Etiocholanediol (5β-androstanediol) may refer to: * 3α-Etiocholanediol (5β-androstane-3α,17β-diol; etiocholane-3α,17β-diol) – an endogenous intermediate to epiandrosterone * 3β-Etiocholanediol (5β-androstane-3β,17β-diol; etiocholane- ...

androstadienol Androstadienol, or androsta-5,16-dien-3β-ol, is a 16-androstene class endogenous steroid, pheromone, and chemical intermediate to several other pheromones that is found in the sweat of both men and women. Androstadienol and androstadienone ...

, and

androstenol Androstenol, also known as 5α-androst-16-en-3α-ol (shortened to 3α,5α-androstenol or 3α-androstenol), is a 16-androstene class steroidal pheromone and neurosteroid in humans and other mammals, notably pigs. It possesses a characteristic mu ...

(and/or their conjugates), and this suggests that only a small amount of pregnenolone is converted into testosterone. This is in accordance with findings on the conversion of

DHEA Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It functio ...

into testosterone, in which only 1.5% of an oral dose of DHEA was found to be converted into testosterone. In contrast to the

androstane Androstane is a C19 steroidal hydrocarbon with a gonane core. Androstane can exist as either of two isomers, known as 5α-androstane and 5β-androstane. File:androstane.png, 5α-Androstane File:androstane 5beta.png, 5β-Androstane Pharmacolog ...

s, 50 or 100 mg oral pregnenolone has been found to significantly and in fact "strongly" increase urinary levels of the progesterone metabolites

pregnanediol Pregnanediol, or 5β-pregnane-3α,20α-diol, is an inactive metabolic product of progesterone. A test can be done to measure the amount of pregnanediol in urine, which offers an indirect way to measure progesterone levels in the body. From the ur ...

and

(and/or their conjugates), whereas

pregnanetriol Pregnanetriol, or 5β-pregnane-3α,17α,20α-triol, is a steroid and inactive metabolite of progesterone. Urine testing Urine excretion of pregnanetriol can be measured over a period of 24 hours. Elevated urine pregnanetriol levels suggest adreno ...

was unaffected. Unlike the case of oral administration,

transdermal administration Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery. The drug is administered in the form of a patch or ointm ...

of 30 mg/day pregnenolone cream has not been found to affect urinary levels of metabolites of any other steroids, including of progesterone.

Intranasal administration Nasal administration, popularly known as snorting, is a route of administration in which drugs are insufflation (medicine), insufflated through the nose. It can be a form of either topical administration or systemic administration, as the drugs t ...

of pregnenolone was found to have low bioavailability of around 23%. Sripada et al. reported that oral pregnenolone is preferentially metabolized into the

rather than into other steroids such as DHEA or

cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

. 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. Pregnanolone levels increased by approximately 60% while DHEA levels decreased non-significantly by approximately 5% and cortisol levels were not affected. 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. In addition to allopregnanolone, pregnenolone acts as a

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

of pregnenolone sulfate. However, pregnenolone sulfate does not cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

Chemistry

Pregnenolone, also known as 5-pregnenolone or as pregn-5-en-3β-ol-20-one, is a

pregnane Pregnane, also known as 17β-ethylandrostane or as 10β,13β-dimethyl-17β-ethylgonane, is a C21 steroid and, indirectly, a parent of progesterone. It is a parent hydrocarbon for two series of steroids stemming from 5α-pregnane (originally all ...

and a

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

. Related steroids include

, 3β-dihydroprogesterone (4-pregnenolone),

progesterone Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...

, and

Derivatives

A few

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

s of pregnenolone exist. These include

pregnenolone acetate Pregnenolone acetate (brand names Antofin, Previsone, Pregno-Pan), also known as pregn-5-en-3β-ol-20-one 3β-acetate, is a synthetic pregnane steroid and an ester of pregnenolone which is described as a glucocorticoid and as a skin-conditioning ...

(Antofin, Previsone, Pregno-Pan) and

pregnenolone succinate Pregnenolone succinate (; brand names Panzalone, Formula 405; also known as pregnenolone hemisuccinate or pregn-5-en-3β-ol-20-one 3β-(hydrogen succinate)) is a synthetic pregnane steroid and an ester of pregnenolone which is described as a gluc ...

(Panzalone, Formula 405).

Prebediolone acetate Prebediolone acetate (brand names Acetoxanon, Acetoxanone, Acetoxy-Prenolon, Artisone, Artivis, Pregnartrone, Sterosone), also known as 21-hydroxypregnenolone 21-acetate or 21-acetoxypregnenolone (A.O.P.), as well as 3β,21-dihydroxypregn-5-en-20 ...

(Acetoxanon, Acetoxy-Prenolon, Artisone, Artivis, Pregnartrone, Sterosone), the 21-

acetate An acetate is a salt formed by the combination of acetic acid with a base (e.g. alkaline, earthy, metallic, nonmetallic, or radical base). "Acetate" also describes the conjugate base or ion (specifically, the negatively charged ion called ...

of 21-hydroxypregnenolone, also exists. These esters are all described as

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

s similarly to pregnenolone. The 3β-

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

ether In organic chemistry, ethers are a class of compounds that contain an ether group, a single oxygen atom bonded to two separate carbon atoms, each part of an organyl group (e.g., alkyl or aryl). They have the general formula , where R and R� ...

of pregnenolone, 3β-methoxypregnenolone (MAP-4343), retains similar activity to pregnenolone in regard to interaction with MAP2, and is under development for potential clinical use for indications such as the treatment of

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

and

spinal cord injury A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. It is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Symptoms of ...

and

depressive disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental disorder, mental and Abnormal behavior, behavioral Disorder (medicine), disorder where the main underlying characteristic is a disturbance in the per ...

History

Pregnenolone was first synthesized by

Adolf Butenandt Adolf Friedrich Johann Butenandt (; 24 March 1903 – 18 January 1995) was a German biochemist. He was awarded the Nobel Prize in Chemistry in 1939 for his "work on sex hormones." He initially rejected the award in accordance with government pol ...

and colleagues in 1934. It was first used in medicine, as an

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...

medication, in the 1940s.

Society and culture

Generic names

''Pregnenolone'' is the generic name of the drug and its , , , and .

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.

Availability

Pregnenolone is no longer marketed as a medication, but remains available as a supplement.

Alternative medicine

Pregnenolone has been promoted online with claims it can treat a variety of diseases including

, and

, but such claims are not backed by evidence.

Research

pregnenolone is being researched for possible therapeutic applications, but its poor

makes its prospects for usefulness low. Pregnenolone is available as an

over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...

, for instance in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

References

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Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemistry, biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or comb ...

, titlestyle = background:#ccccff , list1 = {{Cannabinoid receptor modulators {{Glycine receptor modulators {{Sigma receptor modulators {{Xenobiotic-sensing receptor modulators Abandoned drugs Anti-inflammatory agents CB1 receptor antagonists Glycine receptor agonists Ketones Neurosteroids Pregnane X receptor agonists Pregnanes Prodrugs Secondary alcohols Sigma agonists

Medical uses

Available forms

Pharmacology

Chemistry

Derivatives

History

Society and culture

Generic names

Brand names

Availability

Alternative medicine

Research

See also

References