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Identification
Name Norgestrel
Accession Number DB00506 (APRD00106)
Type small molecule
Groups approved
Description

A synthetic progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Alesse
  • Alpha-Norgestrel
  • Component of Lo/Ovral
  • Component of Ovral
  • DL-Norgestrel
  • LD Norgestrel
  • Ld Norgestrel [French]
  • Lo/Ovral
  • Logynon
  • Methylnorethindrone
  • Microgynon
  • Microlut
  • Monovar
  • Neogest
  • NOG
  • Norgeston
  • Norgestrel [Progestins]
  • Norgestrel [Usan:Ban:Inn:Jan]
  • Norgestrelum [INN-Latin]
  • Ovral
  • Ovran
  • Postinor
  • Stediril
  • Tetragynon
  • Trinordiol
Brand name mixtures
  • Lo-Femenal 21 Tablets (ethinyl estradiol + norgestrel)
  • Ovral 21 Tablets (ethinyl estradiol + norgestrel)
  • Ovral 28 Tablets (ethinyl estradiol + norgestrel)
Categories
  • Contraceptives
  • Contraceptives, Oral, Synthetic
  • Contraceptive Agents, Female
CAS number 6533-00-2
Weight Average: 312.4458
Monoisotopic: 312.208930140
Chemical Formula C21H28O2
InChI Key InChIKey=WWYNJERNGUHSAO-XUDSTZEESA-N
InChI
InChI=1S/C21H28O2/c1-3-20-11-9-17-16-8-6-15(22)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,13,16-19,23H,3,5-12H2,1H3/t16-,17+,18+,19-,20-,21-/m0/s1
Plain Text
IUPAC Name
(1S,2R,10R,11S,14R,15S)-15-ethyl-14-ethynyl-14-hydroxytetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
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 Used as an oral contraceptive to prevent pregnancy
Pharmacodynamics Norgestrel is used as a female contraceptive. Norgestrel is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. Norgestrel tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries.
Mechanism of action Norgestrel binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like Norgestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.
Absorption 65%
Volume of distribution Not Available
Protein binding Norgestrel-binding protein in the plasma appeared to be a protein different from human serum albumin, corticosteroid-binding globulin and sex-steroid-binding protein. High binding (>95%).
Metabolism

Hepatic
Route of elimination Not Available
Half life 5-14 hours
Clearance Not Available
Toxicity Nausea, vomiting, and drowsiness/fatigue; Withdrawal bleeding; LD50=mg/kg (orally in rat)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Insert, extended release Intrauterine
Tablet Oral
Prices
Unit description Cost Unit
Lo/Ovral (28) 28 0.3-30 mg-mcg tablet Disp Pack 62.98 USD disp
Norg-ethin estr 0.5-0.05 mg tablet 5.58 USD tablet
Lo-ovral-8 tablet 2.91 USD tablet
Lo-ovral-28 tablet 2.1 USD tablet
Alesse-28 tablet 1.4 USD tablet
Patents Not Available
Properties
State solid
Melting point 206oC
Experimental Properties
Property Value Source
water solubility 0.00173 mg/mL [PINSUWAN,S et al. (1997)] PhysProp
logP 3.8 PhysProp
Predicted Properties
Property Value Source
water solubility 5.83e-03 g/l ALOGPS
logP 3.25 ALOGPS
logP 3.58 ChemAxon Molconvert
logS -4.73 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 1 ChemAxon Molconvert
refractivity 92.03 ChemAxon Molconvert
polarizability 36.73 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00954 Link_out
KEGG Compound C08153 Link_out
PubChem Compound 13109 Link_out
PubChem Substance 46509177 Link_out
ChemSpider 12560 Link_out
ChEBI 7630 Link_out
ChEMBL 7630 Link_out
Therapeutic Targets Database DAP001208 Link_out
PharmGKB PA450656 Link_out
HET NOG Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic/norgeth.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Norgestrel Link_out
ATC Codes
  • G03AC03
  • G02BA03
AHFS Codes
  • 68:12.00
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.
  • Take at the same time everyday.
  • Take with food.
Targets

1. Progesterone receptor

Pharmacological action: yes
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. Okada H: [Progestogen therapy in the treatment of endometrial cancer—clinical results and mechanism of steroid action] Gan To Kagaku Ryoho. 1988 Apr;15(4 Pt 2-1):924-8. Pubmed
  2. Nielsen ST, Conaty JM, DiPasquale G: Progesterone receptor of adult rabbit lung. Pharmacology. 1987;35(4):217-26. Pubmed
  3. White JO, Moore PA, Marr W, Elder MG, Lim L: Comparative effects of progesterone, norgestrel, norethisterone and tamoxifen on the abnormal uterus of the anovulatory rat. Biochem J. 1982 Oct 15;208(1):199-204. Pubmed
  4. Jeng MH, Parker CJ, Jordan VC: Estrogenic potential of progestins in oral contraceptives to stimulate human breast cancer cell proliferation. Cancer Res. 1992 Dec 1;52(23):6539-46. Pubmed
  5. Corson SL: Efficacy and safety of a monophasic and a triphasic oral contraceptive containing norgestimate. Am J Obstet Gynecol. 1994 May;170(5 Pt 2):1556-61. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Estrogen receptor

Pharmacological action: yes
Actions: agonist

Nuclear hormone receptor. 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: P03372 Link_out
Gene: ESR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Jordan VC, Jeng MH, Catherino WH, Parker CJ: The estrogenic activity of synthetic progestins used in oral contraceptives. Cancer. 1993 Feb 15;71(4 Suppl):1501-5. Pubmed
  2. Yamasaki K, Takeyoshi M, Sawaki M, Imatanaka N, Shinoda K, Takatsuki M: Immature rat uterotrophic assay of 18 chemicals and Hershberger assay of 30 chemicals. Toxicology. 2003 Feb 1;183(1-3):93-115. Pubmed
  3. Yamasaki K, Takeyoshi M, Yakabe Y, Sawaki M, Imatanaka N, Takatsuki M: Comparison of reporter gene assay and immature rat uterotrophic assay of twenty-three chemicals. Toxicology. 2002 Jan 15;170(1-2):21-30. Pubmed
  4. Rabe T, Bohlmann MK, Rehberger-Schneider S, Prifti S: Induction of estrogen receptor-alpha and -beta activities by synthetic progestins. Gynecol Endocrinol. 2000 Apr;14(2):118-26. Pubmed
  5. Jeng MH, Parker CJ, Jordan VC: Estrogenic potential of progestins in oral contraceptives to stimulate human breast cancer cell proliferation. Cancer Res. 1992 Dec 1;52(23):6539-46. 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. Abel S, Russell D, Whitlock LA, Ridgway CE, Muirhead GJ: Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers. Br J Clin Pharmacol. 2008 Apr;65 Suppl 1:19-26. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on May 05, 2011 13:43

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.