U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C27H38O3
Molecular Weight 410.5888
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NORETHINDRONE ENANTHATE

SMILES

[H][C@@]12CC[C@@](OC(=O)CCCCCC)(C#C)[C@@]1(C)CC[C@]3([H])[C@@]4([H])CCC(=O)C=C4CC[C@@]23[H]

InChI

InChIKey=APTGJECXMIKIET-WOSSHHRXSA-N
InChI=1S/C27H38O3/c1-4-6-7-8-9-25(29)30-27(5-2)17-15-24-23-12-10-19-18-20(28)11-13-21(19)22(23)14-16-26(24,27)3/h2,18,21-24H,4,6-17H2,1,3H3/t21-,22+,23+,24-,26-,27-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8520623 https://www.medicines.org.uk/emcmobile/PIL.23891.latest.pdf http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/018405s023lbl.pdf

Norethisterone (INN, BAN), also known as Norethindrone (USAN) (brand names Micronor, AYGESTIN, numerous others) is a synthetic progestational hormone (progestin) with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used for the treatment of secondary amenorrhea, endometriosis, and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer. AYGESTIN® is not intended, recommended or approved to be used with oncomitant estrogen therapy in postmenopausal women for endometrial protection. Progestins diffuse freely into target cells and bind to the progesterone receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH surge. Allergic reaction could be: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing.

CNS Activity

Curator's Comment: Known to be CNS penetrant in rat. Human data not available Norethindrone affects the levels of opioid petides in the rat brain, but it is not clear whether this action is mediated by direct activity within CNS

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
6.8 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
MICRONOR

Approved Use

Indications Progestin-only oral contraceptives are indicated for the prevention of pregnancy. 2. Efficacy If used perfectly, the first-year failure rate for progestin-only oral contraceptives is 0.5%. However, the typical failure rate is estimated to be closer to 5%, due to late or omitted pills. Table 1 lists the pregnancy rates for users of all major methods of contraception. Table 1: Percentage of Women Experiencing an Unintended Pregnancy During the First Year of Typical Use and the First Year of Perfect Use of Contraception and the Percentage Continuing Use at the End of the First Year. United States. Adapted from Hatcher et al, 1998, Ref. #1 Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%The treatment schedule is one dose within 72 hours after unprotected intercourse, and a second dose 12 hours after the first dose. The Food and Drug Administration has declared the following brands of oral contraceptives to be safe and effective for emergency contraception: Ovral® (1 dose is 2 white pills), Alesse® (1 dose is 5 pink pills), Nordette® or Levlen® (1 dose is 2 light-orange pills), Lo/Ovral® (1 dose is 4 white pills), Triphasil ® or Tri-Levlen® (1 dose is 4 yellow pills) Lactational Amenorrhea Method: LAM is highly effective, temporary method of contraceptionHowever, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches six months of age. Source: Trussell J, Contraceptive efficacy. In Hatcher RA, Trussel J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, Contraceptive Technology: Seventeenth Revised Edition. New York NY: Irvington Publishers, 1998. % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One Year Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year Method (1) Typical UseAmong typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason (2) Perfect UseAmong couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason (3) (4) ChanceThe percents becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percent who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether 85 85 SpermicidesFoams, creams, gels, vaginal suppositories, and vaginal film 26 6 40 Periodic abstinence 25 63 Calendar 9 Ovulation Method 3 Sympto-Thermal Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases 2 Post-Ovulation 1 CapWith spermicidal cream or jelly Parous Women 40 26 42 Nulliparous Women 20 9 56 Sponge Parous Women 40 20 42 Nulliparous Women 20 9 56 Diaphragm 20 6 56 Withdrawal 19 4 CondomWithout spermicides Female (Reality®) 21 5 56 Male 14 3 61 Pill 5 71 Progestin Only 0.5 Combined 0.1 IUD Progesterone T 2.0 1.5 81 Copper T380A 0.8 0.6 78 LNg 20 0.1 0.1 81 Depo-Provera® 0.3 0.3 70 Norplant® and Norplant-2® 0.05 0.05 88 Female Sterilization 0.5 0.5 100 Male Sterilization 0.15 0.10 100 Norethindrone tablets have not been studied for and are not indicated for use in emergency contraception.

Launch Date

1973
Primary
AYGESTIN

Approved Use

AYGESTIN® is indicated for the treatment of secondary amenorrhea, endometriosis, and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer. AYGESTIN® is not intended, recommended or approved to be used with concomitant estrogen therapy in postmenopausal women for endometrial protection.

Launch Date

1982
Primary
AYGESTIN

Approved Use

AYGESTIN® is indicated for the treatment of secondary amenorrhea, endometriosis, and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer. AYGESTIN® is not intended, recommended or approved to be used with concomitant estrogen therapy in postmenopausal women for endometrial protection.

Launch Date

1982
Primary
AYGESTIN

Approved Use

AYGESTIN® is indicated for the treatment of secondary amenorrhea, endometriosis, and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer. AYGESTIN® is not intended, recommended or approved to be used with concomitant estrogen therapy in postmenopausal women for endometrial protection.

Launch Date

1982
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
26.19 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORETHINDRONE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
166.9 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORETHINDRONE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.51 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORETHINDRONE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3%
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORETHINDRONE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: FEMALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
15 mg 1 times / day multiple, oral
Studied dose
Dose: 15 mg, 1 times / day
Route: oral
Route: multiple
Dose: 15 mg, 1 times / day
Sources:
unhealthy, 10.2-41.9 years
Health Status: unhealthy
Condition: Endometriosis
Age Group: 10.2-41.9 years
Sex: F
Sources:
Other AEs: Weight gain...
Other AEs:
Weight gain
Sources:
20 uCi single, intravenous
Dose: 20 uCi
Route: intravenous
Route: single
Dose: 20 uCi
Sources:
healthy, 25-35 years
n = 6
Health Status: healthy
Age Group: 25-35 years
Sex: F
Population Size: 6
Sources:
AEs

AEs

AESignificanceDosePopulation
Weight gain
15 mg 1 times / day multiple, oral
Studied dose
Dose: 15 mg, 1 times / day
Route: oral
Route: multiple
Dose: 15 mg, 1 times / day
Sources:
unhealthy, 10.2-41.9 years
Health Status: unhealthy
Condition: Endometriosis
Age Group: 10.2-41.9 years
Sex: F
Sources:
Overview

Overview

Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Induction of estrogen receptor-alpha and -beta activities by synthetic progestins.
2000 Apr
The effect of medroxyprogesterone acetate and norethisterone on the estradiol stimulated proliferation in MCF-7 cells: comparison of continuous combined versus sequential combined estradiol/progestin treatment.
2001
Biphasic versus monophasic oral contraceptives for contraception.
2001
Detection of estrogenicity by bioassay on the mouse mammary gland in vivo.
2001
Counting the costs: comparing depot medroxyprogesterone acetate and norethisterone oenanthate utilisation patterns in South Africa.
2001
Randomized comparison between orally and transdermally administered hormone replacement therapy regimens of long-term effects on 24-hour ambulatory blood pressure in postmenopausal women.
2001 Apr
Effects of hormone replacement therapy and high-impact physical exercise on skeletal muscle in post-menopausal women: a randomized placebo-controlled study.
2001 Aug
Omental pregnancy in a woman taking the progestogen-only pill.
2001 Dec
Solution structure and dynamics of an open beta-sheet, glycolytic enzyme, monomeric 23.7 kDa phosphoglycerate mutase from Schizosaccharomyces pombe.
2001 Feb 16
Charcoal treatment and risk of escape ovulation in oral contraceptive users.
2001 Jan
The effects of sequential combined oral 17beta-estradiol norethisterone acetate on insulin sensitivity and body composition in healthy postmenopausal women: a randomized single blind placebo-controlled study.
2001 Jan-Feb
Metabolism of norethisterone and norethisterone derivatives in rat uterus, vagina, and aorta.
2001 Jul
Comparison of a novel norgestimate/ethinyl estradiol oral contraceptive (Ortho Tri-Cyclen Lo) with the oral contraceptive Loestrin Fe 1/20.
2001 Jun
The effects of transdermal estradiol in combination with oral norethisterone on lipoproteins, coagulation, and endothelial markers in postmenopausal women with type 2 diabetes: a randomized, placebo-controlled study.
2001 Mar
Temporary discontinuation: a compliance issue in injectable users.
2001 Nov
Hormone replacement therapy and acquired resistance to activated protein C: results of a randomized, double-blind, placebo-controlled trial.
2001 Nov
Solution structure and backbone dynamics of an engineered arginine-rich subdomain 2 of the hepatitis C virus NS3 RNA helicase.
2001 Nov 30
A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis in women with progestin-negative functional hypothalamic amenorrhea.
2001 Oct
Effect of conjugated estrogens on free IGF-I?
2001 Sep
Influence of postmenopausal hormone replacement therapy on platelet serotonin uptake site and serotonin 2A receptor binding.
2001 Sep
Unscheduled bleeding during initiation of continuous combined hormone replacement therapy: a direct comparison of two combinations of norethindrone acetate and ethinyl estradiol to medroxyprogesterone acetate and conjugated equine estrogens.
2001 Sep-Oct
An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations.
2002 Feb
Effect of rofecoxib on the pharmacokinetics of chronically administered oral contraceptives in healthy female volunteers.
2002 Feb
Hormone replacement therapy can augment vascular relaxation in post-menopausal women with type 2 diabetes.
2002 Feb
The efficacy of two dosages of a continuous combined hormone replacement regimen.
2002 Feb 26
Patents

Sample Use Guides

Secondary amenorrhea, abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology: 2.5 to 10 mg may be given daily for 5 to 10 days to produce secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen. Endometriosis: Initial daily dosage of 5 mg for two weeks. Dosage should be increased by 2.5 mg per day every two weeks until 15 mg per day.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: Growth of MCF-7 cells was stimulated by norethindrone (10(-8)-10(-5) M), with maximal growth stimulation at 10(-7) M norethindrone after 7 days of treatment
10 - 10000 nM norethindrone stimulates growth of MCF-7 cells
Name Type Language
NORETHINDRONE ENANTHATE
Common Name English
NORETHISTERONE ENANTATE
MART.   WHO-DD   WHO-IP  
Common Name English
NORIGEST
Brand Name English
Norethisterone enantate [WHO-DD]
Common Name English
NSC-22846
Code English
NORETHISTERONE ENANTATE [MART.]
Common Name English
19-NORPREGN-4-EN-20-YN-3-ONE, 17-((1-OXOHEPTYL)OXY)-, (17.ALPHA.)-
Systematic Name English
NORETHISTERONI ENANTAS [WHO-IP LATIN]
Common Name English
SH-8.0393
Code English
NORISTERAT
Brand Name English
NORETHISTERONE ENANTATE [WHO-IP]
Common Name English
ZK-5410
Code English
Classification Tree Code System Code
WHO-ESSENTIAL MEDICINES LIST 18.3.2
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Code System Code Type Description
PUBCHEM
229295
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PRIMARY
ECHA (EC/EINECS)
223-326-7
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PRIMARY
FDA UNII
HY3S2K0J0F
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PRIMARY
SMS_ID
100000085741
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PRIMARY
EVMPD
SUB03458MIG
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PRIMARY
NSC
22846
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PRIMARY
EPA CompTox
DTXSID2048664
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PRIMARY
DRUG BANK
DB14678
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PRIMARY
RXCUI
31984
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PRIMARY RxNorm
DRUG CENTRAL
1964
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PRIMARY
WIKIPEDIA
NORETHINDRONE ENANTHATE
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PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
NORETHINDRONE ENANTHATE
Created by admin on Fri Dec 15 15:04:14 GMT 2023 , Edited by admin on Fri Dec 15 15:04:14 GMT 2023
PRIMARY Description: A white to creamy white, crystalline powder; odourless. Solubility: Practically insoluble in water; freely soluble in acetone R, methanol R, dehydrated ethanol R, dioxan R and ether R; slightly soluble in light petroleum R. Category: Contraceptive. Storage: Norethisterone enantate should be kept in a tightly closed container, protected from light. Requirements: Norethisterone enantate contains not less than 96.0% and not more than the equivalent of 104.0% of C27H38O3, calculated withreference to the dried substance.
CAS
3836-23-5
Created by admin on Fri Dec 15 15:04:14 GMT 2023 , Edited by admin on Fri Dec 15 15:04:14 GMT 2023
PRIMARY
MESH
C024319
Created by admin on Fri Dec 15 15:04:14 GMT 2023 , Edited by admin on Fri Dec 15 15:04:14 GMT 2023
PRIMARY