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Identification
Name Norethindrone
Accession Number DB00717 (APRD00679)
Type small molecule
Groups approved
Description

A synthetic progestational hormone 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 in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Anhydrohydroxynorprogesterone
  • Anovulatorio
  • Anovule
  • Aygestin
  • Binovum
  • Brevicon
  • Brevinor
  • Brevinor 21
  • Brevinor 28
  • Brevinor-1 21
  • Brevinor-1 28
  • Camila
  • Ciclovulan
  • Conceplan
  • Conludaf
  • Conludag
  • Demulen
  • ENT
  • Errin
  • Estrinor
  • Ethinylnortestosterone
  • Ethynylmortestosterone
  • Ethynylnortestosterone
  • Gencept
  • Genora
  • Gestest
  • Jenest
  • Jenest-28
  • Loestrin
  • Loestrin 24 Fe
  • Menzol
  • Microneth
  • Micronett
  • Micronor
  • Micronovum
  • Milli
  • Mini-Pe
  • Mini-Pill
  • Minovlar
  • Modicon
  • N.E.E.
  • Necon
  • Nelova
  • Neocon
  • NET
  • Nodiol
  • Nor-Q.D.
  • Nor-Qd
  • Noraethisteronum
  • Noralutin
  • Norcept
  • Norcept-E
  • Norcolut
  • Noresthisterone
  • Norethadrone
  • Norethin
  • Norethin 1/35 E
  • Norethin 1/50 M
  • Norethindrone Acetate
  • Norethindrone Norethisterone
  • Norethisteron
  • Norethisterone
  • Norethisterone [Progestins]
  • Norethisteronum [INN-Latin]
  • Norethyndron
  • Norethynodron
  • Norethynodrone
  • Noretisterona [INN-Spanish]
  • Noretisterone [Dcit]
  • Norfor
  • Norgestin
  • Noriday
  • Noriday 28
  • Norimin
  • Norinyl
  • Norlestrin
  • Norlutate
  • Norluten
  • Norlutin
  • Norluton
  • Normapause
  • Norpregneninlone
  • Norpregneninolone
  • Norpregneninotone
  • Orlest
  • Ortho 1 35
  • Ortho 7 7 7
  • Ortho-Novum
  • Ortho-Novum 1 35
  • Ortho-Novum 1 50
  • Ortho-Novum 7 7 7
  • Ovcon
  • Ovysmen
  • Ovysmen 0.5 35
  • Ovysmen 1 35
  • Palonyl
  • Perovex
  • Primolut N
  • Primolut-N
  • Proluteasi
  • Synphase
  • Synphasic 28
  • Tri-Norinyl
  • Triella
  • Trinovum
  • Trinovum 21
  • Utovlan
  • Utovlar
Brand name mixtures
  • Brevicon 0.5/35 (21 day) (Ethinyl Estradiol + Norethindrone)
  • Brevicon 0.5/35 (28 day) (Ethinyl Estradiol + Norethindrone)
  • Brevicon 0.5/35 Tablets (21 day) (Ethinyl Estradiol + Norethindrone)
  • Brevicon 0.5/35 Tablets (28 day) (Ethinyl Estradiol + Norethindrone)
  • Brevicon 1/35 Tablets (21 day) (Ethinyl Estradiol + Norethindrone)
  • Brevicon 1/35 Tablets (28 day) (Ethinyl Estradiol + Norethindrone)
  • Estalis 140/50 Mcg (Estradiol + Norethindrone Acetate)
  • Estalis 250/50 Mcg (Estradiol + Norethindrone Acetate)
  • Estalis Sequi (Estradiol + Norethindrone Acetate)
  • Estracomb (Estradiol + Norethindrone Acetate)
  • Femhrt 1/5 (Ethinyl Estradiol + Norethindrone Acetate)
  • Loestrin 1.5/30 21-day Pack (Ethinyl Estradiol + Norethindrone Acetate)
  • Loestrin 1.5/30 28-day Pack (Ethinyl Estradiol + Norethindrone Acetate)
  • Minestrin 1/20 21 (Ethinyl Estradiol + Norethindrone Acetate)
  • Minestrin 1/20 28 (Ethinyl Estradiol + Norethindrone Acetate)
  • Norinyl 1/50 - 21-day pack (Mestranol + Norethindrone)
  • Norinyl 1/50 - 28-day pack (Mestranol + Norethindrone)
  • Norinyl 1/50 (21 day) (Mestranol + Norethindrone)
  • Norinyl 1/50 (28 day) (Mestranol + Norethindrone)
  • Ortho 0.5/35 Tablets (21 day) (Ethinyl Estradiol + Norethindrone)
  • Ortho 0.5/35 Tablets (28 day) (Ethinyl Estradiol + Norethindrone)
  • Ortho 1/35 Tablets (21 day) (Ethinyl Estradiol + Norethindrone)
  • Ortho 1/35 Tablets (28 day) (Ethinyl Estradiol + Norethindrone)
  • Ortho 10/11 Tablets (21 day) (Ethinyl Estradiol + Norethindrone)
  • Ortho 10/11 Tablets (28 day) (Ethinyl Estradiol + Norethindrone)
  • Ortho 7/7/7 Tablets (21 day) (Ethinyl Estradiol + Norethindrone)
  • Ortho 7/7/7 Tablets (28 day) (Ethinyl Estradiol + Norethindrone)
  • Ortho-Novum 1/50 Tablets (21 day) (Mestranol + Norethindrone)
  • Ortho-Novum 1/50 Tablets (28 day) (Mestranol + Norethindrone)
  • Select 1/35 (21 day) (Ethinyl Estradiol + Norethindrone)
  • Select 1/35 (28 day) (Ethinyl Estradiol + Norethindrone)
  • Synphasic (21 day) (Ethinyl Estradiol + Norethindrone)
  • Synphasic (28 day) (Ethinyl Estradiol + Norethindrone)
Categories
  • Contraceptives, Oral, Synthetic
  • Progestins
CAS number 68-22-4
Weight Average: 298.4192
Monoisotopic: 298.193280076
Chemical Formula C20H26O2
InChI Key InChIKey=VIKNJXKGJWUCNN-XGXHKTLJSA-N
InChI
InChI=1S/C20H26O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,12,15-18,22H,4-11H2,2H3/t15-,16+,17+,18-,19-,20-/m0/s1
Plain Text
IUPAC Name
(1S,2R,10R,11S,14R,15S)-14-ethynyl-14-hydroxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]
Plain Text
Mass Spec show (11.3 KB)
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Alkynes
  • Alcohols and Polyols
  • Cyclohexenes and Derivatives
  • Ketones
Pharmacology
Indication For use as an oral contraceptive in the prevention of pregnancy.
Pharmacodynamics Norethindrone is a synthetic oral progestin. It is used for contraception or to treat such conditions as secondary amenorrhea, abnormal uterine bleeding, and endometriosis. As an oral contraceptive, norethindrone is available as either a single agent or in combination with an estrogen.
Mechanism of action 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.
Absorption Absolute oral bioavailability approximately 64%
Volume of distribution Not Available
Protein binding >95%
Metabolism

Hepatic
Route of elimination Not Available
Half life 7 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Parke davis div warner lambert co
  • Barr laboratories inc
  • Glenmark generics ltd
  • Ortho mcneil janssen pharmaceuticals inc
  • Watson laboratories inc
  • Duramed research inc
  • Glenmark generics ltd india
  • Warner Chilcott
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Ovcon-35 (28) 28 0.4-35 mg-mcg tablet Disp Pack 89.09 USD disp
Ovcon-50 28 50-1 mcg-mg tablet Disp Pack 89.09 USD disp
Loestrin 1.5/30 (21) 21 1.5-30 mg-mcg tablet Disp Pack 79.32 USD disp
Loestrin 1/20 (21) 21 1-20 mg-mcg tablet Disp Pack 79.32 USD disp
Loestrin Fe 1/20 28 1-20 mg-mcg tablet Disp Pack 79.32 USD disp
Loestrin Fe 1.5/30 28 1.5-30 mg-mcg tablet Disp Pack 77.1 USD disp
Loestrin 24 Fe 28 1-20 mg-mcg tablet Disp Pack 75.15 USD disp
Nor-QD 28 0.35 mg tablet Disp Pack 65.87 USD disp
Tri-Norinyl (28) 28 0.5/1/0.5-35 mg-mcg tablet Disp Pack 62.63 USD disp
Ortho-Novum 10/11 (28) 28 35 mcg tablet Disp Pack 60.25 USD disp
Modicon (28) 28 0.5-35 mg-mcg tablet Disp Pack 59.99 USD disp
Norinyl 1+35 (28) 28 1-35 mg-mcg tablet Disp Pack 55.99 USD disp
Ortho-Novum 1/35 (28) 28 1-35 mg-mcg tablet Disp Pack 55.99 USD disp
Brevicon (28) 28 0.5-35 mg-mcg tablet Disp Pack 53.0 USD disp
Norinyl 1+50 (28) 28 1-50 mg-mcg tablet 1 Disp Pack = 28 Pills 52.99 USD disp
Necon 10/11 (28) 28 35 mcg tablet Disp Pack 35.99 USD disp
Ortho-Novum 7/7/7 (28) 28 0.5/0.75/1-35 mg-mcg tablet Disp Pack 33.99 USD disp
Necon 0.5/35 (28) 28 0.5-35 mg-mcg tablet Disp Pack 32.99 USD disp
Necon 1/35 (28) 28 1-35 mg-mcg tablet Disp Pack 31.99 USD disp
Loestrin fe 1-20 tablet 5.23 USD tablet
Loestrin 21 1.5-30 tablet 3.66 USD tablet
Loestrin 21 1-20 tablet 3.66 USD tablet
Aygestin 5 mg tablet 3.27 USD tablet
Ovcon-35 28 tablet 3.06 USD tablet
Loestrin fe 1.5-30 tablet 2.75 USD tablet
Norethindrone Acetate 5 mg tablet 2.75 USD tablet
Norethindrone 5 mg tablet 2.65 USD tablet
Ovcon-50 28 tablet 2.62 USD tablet
Micronor tablet 2.44 USD tablet
Nor-q-d tablet 2.24 USD tablet
Necon 1-35-28 tablet 2.11 USD tablet
Modicon 28 tablet 2.07 USD tablet
Tri-norinyl 28 tablet 2.01 USD tablet
Ortho-novum 1-35-28 tablet 1.9 USD tablet
Brevicon 28 tablet 1.8 USD tablet
Norinyl 1+35-28 tablet 1.73 USD tablet
Norinyl 1+50-28 tablet 1.73 USD tablet
Demulen 1-50-21 tablet 1.67 USD tablet
Ortho-novum 7-7-7-21 tablet 1.4 USD tablet
Errin 0.35 mg tablet 1.34 USD tablet
Ortho-novum 7/7/7-28 tablet 1.33 USD tablet
Camila tablet 1.32 USD tablet
Jolivette tablet 1.32 USD tablet
Nora-be tablet 1.32 USD tablet
Norethindrone 0.35 mg tablet 1.32 USD tablet
Demulen 1-50-28 tablet 1.29 USD tablet
Ortho micronor tablet 1.23 USD tablet
Necon 0.5-35-28 tablet 1.15 USD tablet
Necon 7-7-7-28 tablet 1.15 USD tablet
Necon 1-50-28 tablet 1.05 USD tablet
Ortho-novum 7-7-7-28 tablet 1.02 USD tablet
Micronor (28 Day) 0.35 mg Tablet 0.66 USD tablet
Patents Not Available
Properties
State solid
Melting point 203.5 oC
Experimental Properties
Property Value Source
water solubility 7.04 mg/L PhysProp
logP 3.2 PhysProp
logS -4.57 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 6.68e-03 g/l ALOGPS
logP 2.72 ALOGPS
logP 3.13 ChemAxon Molconvert
logS -4.65 ALOGPS
pKa 19.28 ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 37.30 ChemAxon Molconvert
rotatable bond count 0 ChemAxon Molconvert
refractivity 87.42 ChemAxon Molconvert
polarizability 34.71 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00182 Link_out
KEGG Compound C05028 Link_out
PubChem Compound 6230 Link_out
PubChem Substance 46504816 Link_out
ChemSpider 5994 Link_out
ChEBI 7627 Link_out
ChEMBL 7627 Link_out
Therapeutic Targets Database DAP001212 Link_out
PharmGKB PA450651 Link_out
HET NDR Link_out
Drug Product Database 23760 Link_out
RxList http://www.rxlist.com/cgi/generic2/norethin.htm Link_out
Drugs.com http://www.drugs.com/cdi/norethindrone.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ayg1666.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Norethindrone Link_out
ATC Codes
  • G03AC01
AHFS Codes
  • 68:12.00
PDB Entries Not Available
FDA label show (321.9 KB)
MSDS show (73.9 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Targets

1. Progesterone receptor

Pharmacological action: unknown
Actions: agonist

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues

Organism class: human
UniProt ID: P06401 Link_out
Gene: PGR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mendoza-Rodriguez CA, Camacho-Arroyo I, Garcia GA, Cerbon MA: Variations of progesterone receptor and c-fos gene expression in the rat uterus after treatment with norethisterone and its A-ring reduced metabolites. Contraception. 1999 May;59(5):339-43. Pubmed
  2. Madauss KP, Deng SJ, Austin RJ, Lambert MH, McLay I, Pritchard J, Short SA, Stewart EL, Uings IJ, Williams SP: Progesterone receptor ligand binding pocket flexibility: crystal structures of the norethindrone and mometasone furoate complexes. J Med Chem. 2004 Jun 17;47(13):3381-7. Pubmed
  3. Garcia-Becerra R, Cooney AJ, Borja-Cacho E, Lemus AE, Perez-Palacios G, Larrea F: Comparative evaluation of androgen and progesterone receptor transcription selectivity indices of 19-nortestosterone-derived progestins. J Steroid Biochem Mol Biol. 2004 Jun;91(1-2):21-7. Pubmed
  4. Mirkin S, Wong BC, Archer DF: Effect of 17 beta-estradiol, progesterone, synthetic progestins, tibolone, and tibolone metabolites on vascular endothelial growth factor mRNA in breast cancer cells. Fertil Steril. 2005 Aug;84(2):485-91. Pubmed
  5. Pasapera AM, Cerbon MA, Castro I, Gutierrez R, Camacho-Arroyo I, Garcia GA, Perez-Palacios G: Norethisterone metabolites modulate the uteroglobin and progesterone receptor gene expression in prepubertal rabbits. Biol Reprod. 1995 Feb;52(2):426-32. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A7

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C19

Actions: inducer

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kim WY, Benet LZ: P-glycoprotein (P-gp/MDR1)-mediated efflux of sex-steroid hormones and modulation of P-gp expression in vitro. Pharm Res. 2004 Jul;21(7):1284-93. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:05

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.