Noretynodrel, or norethynodrel, sold under the brand name Enovid among others, is a

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...

medication which was previously used in

birth control pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progest ...

s and in the treatment of

gynecological disorder Gynaecology or gynecology (see spelling differences) is the area of medicine that involves the treatment of women's diseases, especially those of the reproductive organs. It is often paired with the field of obstetrics, forming the combined area ...

s but is now no longer marketed. It was available both alone and in combination with an

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

. The medication is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. Noretynodrel is a progestin, or a synthetic

progestogen Progestogens, also sometimes written 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 progestogen in the body. ...

, and hence is an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the

progesterone receptor The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single ''PGR'' gene resid ...

, the

biological target A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...

of progestogens like

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 m ...

. It is a relatively weak progestogen. The medication has weak

ic activity, no or only very weak

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

ic activity, and no other important

hormonal A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required fo ...

activity. It is a

prodrug A prodrug is a 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 used to improve how the drug ...

of various

active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...

s in the body, such as

norethisterone Norethisterone, also known as norethindrone and sold under many brand names, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in both ...

among others. Noretynodrel was introduced for medical use in 1957. It was specifically approved at this time in combination with

mestranol Mestranol, sold under the brand names Enovid, Norinyl, and Ortho-Novum among others, is an estrogen medication which has been used in birth control pills, menopausal hormone therapy, and the treatment of menstrual disorders. It is formulated in c ...

for the treatment of

gynecological Gynaecology or gynecology (see spelling differences) is the area of medicine that involves the treatment of women's diseases, especially those of the reproductive organs. It is often paired with the field of obstetrics, forming the combined area ...

and

menstrual disorder A menstrual disorder is characterized as any abnormal condition with regards to a person's menstrual cycle. There are many different types of menstrual disorders that vary with signs and symptoms, including pain during menstruation, heavy bleeding ...

s. Subsequently, in 1960, this formulation was approved for use as a birth control pill. It was the first birth control pill to be introduced, and was followed by birth control pills containing norethisterone and other progestins shortly thereafter. Due to its nature as a relatively weak progestogen, noretynodrel is no longer used in medicine. As such, it is no longer marketed.

Medical uses

Noretynodrel was formerly used in combination with the

in the treatment of

and

s and as a

combined birth control pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progesti ...

. It has also been used in the treatment of

endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, f ...

at high dosages of 40 to 100 mg/day. The medication has been discontinued, and is no longer marketed or used medically.

Contraindications

No adverse effects have been observed in

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

infants whose mothers were treated with noretynodrel. Because of this, the

American Academy of Pediatrics The American Academy of Pediatrics (AAP) is an American professional association of pediatricians, headquartered in Itasca, Illinois. It maintains its Department of Federal Affairs office in Washington, D.C. Background The Academy was founded ...

has considered noretynodrel to be usually compatible with breastfeeding.

Side effects

There is a reported case of signs of

masculinization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and biology ...

in a female infant whose mother was treated with noretynodrel for threatened miscarriage during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

Overdose

Interactions

Pharmacology

Pharmacodynamics

Noretynodrel has weak

ic activity, weak

ic activity, and no or only very weak

ic activity. It is considered to be a

, and for this reason, the

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 of noretynodrel play an important role in its

biological activity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...

. As such, the

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

of noretynodrel cannot be understood without reference to its

metabolism Metabolism (, from el, μεταβολή ''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 cell ...

. Noretynodrel is closely related to norethisterone and tibolone, which are the δ⁴-isomer and the 7α-

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 . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...

derivative of noretynodrel, respectively. It is metabolized in a very similar manner to tibolone, whereas the metabolism of norethisterone differs. Both noretynodrel and tibolone are transformed into 3α- and 3β-hydroxylated metabolites and a δ⁴-isomer metabolite (in the case of noretynodrel, this being norethisterone), whereas norethisterone is not 3α- or 3β-hydroxylated (and of course does not form a δ⁴-isomer metabolite). The major

s of noretynodrel are 3α-hydroxynoretynodrel and to a lesser extent 3β-hydroxynoretynodrel, formed respectively by 3α- and 3β-hydroxysteroid dehydrogenases (

AKR1C1 Aldo-keto reductase family 1 member C1 also known as 20α-hydroxysteroid dehydrogenase, 3α-hydroxysteroid dehydrogenase, and dihydrodiol dehydrogenase 1/2 is an enzyme that in humans is encoded by the ''AKR1C1'' gene. This gene encodes a member ...

– 4), while the δ⁴-isomer norethisterone is a minor metabolite formed in small amounts. Tibolone is considered to be a prodrug of both its 3α- and 3β-hydroxylated and δ⁴-isomerized metabolites. Noretynodrel is also thought to be a prodrug, as it is rapidly metabolized and cleared from circulation and shows very weak relative affinity for the

(PR), although it appears to form norethisterone in only minor quantities.

Progestogenic activity

Noretynodrel is a relatively weak

, with only about one-tenth of the progestogenic activity of norethisterone. The

ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized ...

-inhibiting dosage of noretynodrel is 4.0 mg/day, relative to 0.4 mg/day in the case of norethisterone. Conversely, the endometrial transformation dosage of noretynodrel is 150 mg per cycle, relative to 120 mg per cycle for norethisterone. In terms of the PR, noretynodrel possesses only about 6 to 19% of the

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

of norethisterone for the PR_A, whereas the affinity of the two drugs for the PR_B is similar (noretynodrel possesses 94% of the affinity of norethisterone for the PR_B). Tibolone and the δ⁴-isomer metabolite of tibolone have similar affinity for the PRs as noretynodrel and norethisterone, respectively, whereas the 3α- and 3β-hydroxylated metabolites of tibolone are virtually devoid of affinity for the PRs. Since the structurally related

anabolic steroid Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone (medication), testosterone as well as synthetic androgens that are structurally related ...

trestolone Trestolone, also known as 7α-methyl-19-nortestosterone (MENT), is an experimental androgen/ anabolic steroid (AAS) and progestogen medication which has been under development for potential use as a form of hormonal birth control for men and i ...

(7α-methyl-19-nortestosterone) is known to be a potent progestogen, suggesting that a 7α-methyl substitution does not interfere with progestogenic activity, 3α- and 3β-hydroxynoretynodrel likely are devoid of affinity for the PR similarly to the 3α- and 3β-hydroxylated metabolites of tibolone.

Androgenic activity

Noretynodrel has been said to possess no or only very weak

ic activity. This is in contrast to norethisterone, which shows mild but significant androgenicity. Relative to norethisterone, noretynodrel has 45 to 81% lower affinity for the

androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...

(AR). In accordance, no androgenic effects (such as

hirsutism Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...

clitoral enlargement Clitoromegaly (or macroclitoris) is an abnormal enlargement of the clitoris that is mostly congenital or acquired, though deliberately induced clitoris enlargement as a form of genital body modification is achieved through various uses of anabo ...

, or

voice change ' A voice change or voice mutation, sometimes referred to as a voice break or voice crack, commonly refers to the deepening of the voice of men as they reach puberty. Before puberty, both sexes have roughly similar vocal pitch, but during puberty ...

s) have been observed with noretynodrel even when used in large dosages (e.g., 60 mg/day) for prolonged periods of time (9–12 months) in the treatment of women with

. Additionally, noretynodrel has not been found to virilize female

fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...

es, in contrast to many other

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

-derived progestins including

ethisterone Ethisterone, also known as ethinyltestosterone, pregneninolone, and anhydrohydroxyprogesterone and formerly sold under the brand names Proluton C and Pranone among others, is a progestin medication which was used in the treatment of gynecologica ...

, norethisterone, and

norethisterone acetate Norethisterone acetate (NETA), also known as norethindrone acetate and sold under the brand name Primolut-Nor among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gyn ...

. However, at least one case of

pseudohermaphroditism Pseudohermaphroditism is a condition in which an individual has a matching chromosomal and gonadal tissue (ovary or testis) sex, but mismatching external genitalia. Female pseudohermaphroditism refers to an individual with ovaries and external gen ...

(virilized genitalia) has been observed that may have been due to noretynodrel. The δ⁴-isomer metabolite of tibolone shows dramatically and disproportionately increased affinity for the AR relative to norethisterone and noretynodrel (5.7- to 18.5-fold greater than that of norethisterone), indicating that the 7α-methyl group of tibolone markedly increases its androgenic activity and is responsible for the greater androgenic effects of tibolone relative to noretynodrel.

Estrogenic activity

Noretynodrel, unlike most progestins but similarly to

etynodiol diacetate Etynodiol diacetate, or ethynodiol diacetate, sold under the brand names Demulen and Femulen among others, is a progestin medication which is used in birth control pills. The medication is available only in combination with an estrogen. It is tak ...

, has some

ic activity. Relative to other 19-nortestosterone progestins, noretynodrel is said to possess much stronger estrogenic activity. In the Allen–Doisy test of estrogenicity in animals, noretynodrel has been reported to possess 100-fold greater estrogenic activity than norethisterone. Whereas norethisterone has virtually no affinity for the

estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...

s (ERs), noretynodrel shows some, albeit very weak affinity for both the

ERα Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex ...

and the

ERβ Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by ...

(in terms of

relative binding affinity In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a mol ...

, 0.7% and 0.22% of that of

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...

, respectively). The estrogenic activity of 3α- and 3β-hydroxynoretynodrel has never been assessed. However, while tibolone shows similar affinity for the ERs as noretynodrel, the 3α- and 3β-hydroxylated metabolites of tibolone have several-fold increased affinity for the ERs. As such, the 3α- and 3β-hydroxylated metabolites of noretynodrel may also show increased estrogenic activity, and this may account for the known estrogenic effects of noretynodrel. The δ⁴-isomer of tibolone, similarly to norethisterone, is virtually devoid of affinity for the ERs. Neither tibolone nor its metabolites are aromatized, whereas trestolone is readily aromatized similarly to testosterone and 19-nortestosterone, and for these reasons, it is unlikely that noretynodrel or its metabolites, aside from norethisterone, are aromatized either. As such, aromatization likely does not play a role in the estrogenic activity of tibolone or noretynodrel. However, controversy on this matter exists, and other researchers have suggested that tibolone and noretynodrel may be aromatized in small amounts to highly potent estrogens (

ethinylestradiol Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disord ...

and its 7α-methyl derivative, respectively).

Pharmacokinetics

Noretynodrel is rapidly absorbed upon

oral administration Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are in ...

and is rapidly

metabolized Metabolism (, from el, μεταβολή ''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 cell ...

, disappearing from the circulation within 30 minutes. In terms of

plasma protein binding Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse th ...

, noretynodrel is bound to

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...

, and show no

itself for

sex hormone-binding globulin Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it has also been called androgen ...

corticosteroid-binding globulin Transcortin, also known as corticosteroid-binding globulin (CBG) or serpin A6, is a protein produced in the liver in animals. In humans it is encoded by the SERPINA6 gene. It is an alpha-globulin. Function This gene encodes an alpha-globulin pro ...

. The plasma protein binding of its

s, such as

, may differ however. The major metabolites of noretynodrel in the circulation are 3α-hydroxynoretynodrel (formed by ) and to a lesser extent 3β-hydroxynoretynodrel (formed by ), and more minor metabolites of noretynodrel are

(formed by δ^5-4-isomerase) and possibly

(formed by

aromatase Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many ...

or possibly other

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s, most likely

monooxygenase Monooxygenases are enzymes that incorporate one hydroxyl group (−OH) into substrates in many metabolic pathways. In this reaction, the two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation o ...

s). Due to its very short

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

and its low affinities for

steroid hormone receptor Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors (typically cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which ...

s in receptor binding assays, noretynodrel is considered to be a

which is rapidly transformed into its

s in the

intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...

s and

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

following oral administration. Some researchers have stated that it is specifically a prodrug of norethisterone. According to other researchers however, there is, due to a lack of research, insufficient data to unequivocally show this to be the case at present. About 1% of an oral dose of noretynodrel is detected in

breast milk Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates ( lacto ...

. The

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

of noretynodrel have been reviewed.

Chemistry

Noretynodrel, also known as 17α-ethynyl-δ⁵⁽¹⁰⁾-19-nortestosterone or as 17α-ethynylestr-5(10)-en-17β-ol-3-one, is a synthetic

estrane Estrane is a C18 steroid derivative, with a gonane core. ''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. '' Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, fo ...

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

and a

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. F ...

. It is specifically a derivative of testosterone that has been

ethynyl In organic chemistry, the term ethynyl designates a functional group with a double bond with 2 carbon atoms both with sp hybridisation and a triple bond(1 sigma and 2 pi bond) . It is a species similar to acetylene (or in IUPAC ethyne ) with a less ...

ated at the C17α position,

demethyl In chemical nomenclature, nor- is a prefix to name a structural analog that can be derived from a parent compound by the removal of one carbon atom along with the accompanying hydrogen atoms. The nor-compound can be derived by removal of a , , or ...

ated at the C19 position, and

dehydrogenated In chemistry, dehydrogenation is a chemical reaction that involves the removal of hydrogen, usually from an organic molecule. It is the reverse of hydrogenation. Dehydrogenation is important, both as a useful reaction and a serious problem. At ...

(i.e., has a

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...

) between the C5 and C10 positions). As such, noretynodrel is also a combined derivative of

nandrolone Nandrolone, also known as 19-nortestosterone, is an androgen and anabolic steroid (AAS) which is used in the form of esters such as nandrolone decanoate (brand name Deca-Durabolin) and nandrolone phenylpropionate (brand name Durabolin). Nandrolon ...

(19-nortestosterone) and

(17α-ethynyltestosterone). In addition, it is an

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

of norethisterone (17α-ethynyl-19-nortestosterone) in which the C4 double bond has been replaced with a double bond between the C5 and C10 positions. For this reason, noretynodrel is also known as 5(10)-norethisterone. Few other 19-nortestosterone progestins share the C5(10) double bond of noretynodrel, but examples of a couple that do include

tibolone Tibolone, sold under the brand name Livial among others, is a medication which is used in menopausal hormone therapy and in the treatment of postmenopausal osteoporosis and endometriosis. The medication is available alone and is not formulated ...

, the C7α

derivative of noretynodrel (i.e., 7α-methylnoretynodrel), and

norgesterone Norgesterone, also known as norvinodrel or vinylestrenolone and sold under the brand name Vestalin, is a progestin medication which was formerly used in birth control pills for women but is now no longer marketed. It was used in combination with ...

, the C17α

vinyl Vinyl may refer to: Chemistry * Polyvinyl chloride (PVC), a particular vinyl polymer * Vinyl cation, a type of carbocation * Vinyl group, a broad class of organic molecules in chemistry * Vinyl polymer, a group of polymers derived from vinyl m ...

analogue of noretynodrel.

Synthesis

Chemical syntheses of noretynodrel have been published.

History

Noretynodrel was first synthesized by

Frank B. Colton Frank Benjamin Colton (March 3, 1923 – November 25, 2003), American chemist who first synthesized noretynodrel, the progestin used in Enovid, the first oral contraceptive, at G. D. Searle & Company in Skokie, Illinois in 1952. Biography Frank ...

of G. D. Searle & Company in 1952, and this was preceded by the synthesis of norethisterone by

Luis E. Miramontes Luis Ernesto Miramontes Cárdenas (March 16, 1925 – September 13, 2004) was a Mexican chemist known as the co-inventor of the progestin norethisterone used in one of the first three oral contraceptives. Miramontes was born in Tepic, Nayarit ...

and

Carl Djerassi Carl Djerassi (October 29, 1923 – January 30, 2015) was an Austrian-born Bulgarian-American pharmaceutical chemist, novelist, playwright and co-founder of Djerassi Resident Artists Program with Diane Middlebrook, Diane Wood Middlebrook. He is b ...

of Syntex in 1951. In 1957, both noretynodrel and norethisterone, in combination with

, were approved in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

for the treatment of

s. In 1960, noretynodrel, in combination with mestranol (as ''Enovid''), was introduced in the United States as the first oral contraceptive, and the combination of norethisterone and mestranol followed in 1963 as the second oral contraceptive to be introduced. In 1988, Enovid, along with other oral contraceptives containing high doses of estrogen, was discontinued. Noretynodrel was first studied in the treatment of

in 1961 and was the first progestin to be investigated for the treatment of the condition.

Society and culture

Generic names

''Noretynodrel'' is the of the drug while ''norethynodrel'' is its and . It is also known by its developmental code name ''SC-4642''.

Brand names

Noretynodrel has been marketed by alone under the brand names Enidrel, Orgametril, and Previson and in combination with

under the brand names Conovid, Conovid E, Enavid, Enavid E, Enovid, Enovid E, Norolen, and Singestol.

Availability

Noretynodrel is no longer available in any formulation in the U.S., nor does it appear to still be marketed in any other country.
/ref>

References

{{Navboxes , title =

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

, titlestyle = background:#ccccff , list1 = {{Androgen receptor modulators {{Progesterone receptor modulators {{Estrogen receptor modulators Abandoned drugs Ethynyl compounds Alkene derivatives Androgens and anabolic steroids Estranes Hormonal contraception Ketones Progestogens Synthetic estrogens