Identification

Name
Norgestrel
Accession Number
DB09389
Type
Small Molecule
Groups
Approved
Description

Norgestrel is synthetic steroidal progestin that is used in combination with ethinyl estradiol for oral contraception. Norgestrel is composed of a racemic mixture of two stereoisomers, dextronorgestrel and levonorgestrel. However, only the levorotary enantiomer (levonorgestrel) is biologically active.

Structure
Thumb
Synonyms
  • 17-ethynyl-17-hydroxy-18a-homoestr-4-en-3-one
  • LD norgestrel
  • Methylnorethindrone
  • norgestrel
External IDs
WY 3707 / WY-3707 / WY3707
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ovrette TabletsTablet0.075 mgOralPfizerNot applicableNot applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
CryselleNorgestrel (0.3 mg/1) + Ethinylestradiol (0.03 mg/1)KitA-S Medication Solutions2002-07-24Not applicableUs
CryselleNorgestrel (0.3 mg/1) + Ethinylestradiol (0.03 mg/1)KitTeva2002-07-24Not applicableUs00555 9049 58 nlmimage10 4236a175
CryselleNorgestrel (0.3 mg/1) + Ethinylestradiol (0.03 mg/1)KitRemedy Repack2018-05-17Not applicableUs
CryselleNorgestrel (0.3 mg/1) + Ethinylestradiol (0.03 mg/1)KitPhysicians Total Care, Inc.2003-10-16Not applicableUs54868 485120180907 15195 1xobe06
ElinestNorgestrel (0.3 mg/1) + Ethinylestradiol (0.03 mg/1)KitNorthStar Rx LLC2012-01-07Not applicableUs
Lo-femenal 21 TabletsNorgestrel (300 mcg) + Ethinylestradiol (30 mcg)TabletOralPfizer2001-05-142014-04-04Canada
Lo-ovral-28Norgestrel (0.3 mg/1) + Ethinylestradiol (0.03 mg/1)KitPhysicians Total Care, Inc.1976-03-012012-06-30Us
Lo/OvralNorgestrel (0.3 mg/1) + Ethinylestradiol (0.03 mg/1)TabletOralWyeth Ltd.1975-04-012008-12-31Us
Lo/ovral-28Norgestrel (0.3 mg/1) + Ethinylestradiol (0.03 mg/1)KitWyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.1976-03-012010-12-31Us
Lo/Ovral-28Norgestrel (0.3 mg/1) + Ethinylestradiol (0.03 mg/1)KitAkrimax Pharmaceuticals, LLC1976-03-012014-05-01Us
Categories
UNII
3J8Q1747Z2
CAS number
6533-00-2
Weight
Average: 312.453
Monoisotopic: 312.208930142
Chemical Formula
C21H28O2
InChI Key
WWYNJERNGUHSAO-UHFFFAOYSA-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
IUPAC Name
15-ethyl-14-ethynyl-14-hydroxytetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-5-one
SMILES
CCC12CCC3C(CCC4=CC(=O)CCC34)C1CCC2(O)C#C

Pharmacology

Indication

Norgestrel in combination with ethinyl estradiol is indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception.

Associated Conditions
Associated Therapies
Pharmacodynamics
Not Available
Mechanism of action

Norgestrel (and more specifically the active stereoisomer levonorgestrel) binds to the progesterone and estrogen receptors within the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like levonorgestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. Loss of the LH surge inhibits ovulation and thereby prevents pregnancy.

TargetActionsOrganism
AProgesterone receptor
binder
Human
A3-oxo-5-alpha-steroid 4-dehydrogenase 1
inhibitor
Human
UAndrogen receptor
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinNorgestrel may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinNorgestrel may decrease the anticoagulant activities of (S)-Warfarin.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Norgestrel.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Norgestrel.
5-androstenedioneThe metabolism of Norgestrel can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Norgestrel can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Norgestrel.
AbciximabNorgestrel may decrease the anticoagulant activities of Abciximab.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Norgestrel.
AbirateroneThe metabolism of Norgestrel can be decreased when combined with Abiraterone.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D00954
PubChem Compound
4542
PubChem Substance
347827838
ChemSpider
4383
ChEBI
7630
ChEMBL
CHEMBL2107797
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Norgestrel
ATC Codes
G03FB01 — Norgestrel and estrogenG03FA10 — Norgestrel and estrogenG03AA06 — Norgestrel and ethinylestradiol
AHFS Codes
  • 68:12.00 — Contraceptives
FDA label
Download (6.67 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedPreventionEndometrial Cancers1
2RecruitingTreatmentContraception1
3Active Not RecruitingOtherContraception1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit
KitOral
TabletOral
TabletOral0.075 mg
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00583 mg/mLALOGPS
logP3.25ALOGPS
logP3.66ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)17.91ChemAxon
pKa (Strongest Basic)-1.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity92.03 m3·mol-1ChemAxon
Polarizability36.83 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-2924000000-eb357f64cb0652555ccb

Taxonomy

Description
This compound belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Estrane steroids
Direct Parent
Estrogens and derivatives
Alternative Parents
3-oxo delta-4-steroids / 17-hydroxysteroids / Delta-4-steroids / Cyclohexenones / Ynones / Tertiary alcohols / Cyclic alcohols and derivatives / Acetylides / Organic oxides / Hydrocarbon derivatives
Substituents
Estrogen-skeleton / 3-oxo-delta-4-steroid / 3-oxosteroid / 17-hydroxysteroid / Oxosteroid / Hydroxysteroid / Delta-4-steroid / Cyclohexenone / Ynone / Cyclic alcohol
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
terminal acetylenic compound, 3-oxo steroid, 17-hydroxy steroid (CHEBI:7630)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Hammond GL, Rabe T, Wagner JD: Preclinical profiles of progestins used in formulations of oral contraceptives and hormone replacement therapy. Am J Obstet Gynecol. 2001 Aug;185(2 Suppl):S24-31. [PubMed:11521119]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Electron carrier activity
Specific Function
Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and andro...
Gene Name
SRD5A1
Uniprot ID
P18405
Uniprot Name
3-oxo-5-alpha-steroid 4-dehydrogenase 1
Molecular Weight
29458.18 Da
References
  1. Rabe T, Kowald A, Ortmann J, Rehberger-Schneider S: Inhibition of skin 5 alpha-reductase by oral contraceptive progestins in vitro. Gynecol Endocrinol. 2000 Aug;14(4):223-30. [PubMed:11075290]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Kloosterboer HJ, Vonk-Noordegraaf CA, Turpijn EW: Selectivity in progesterone and androgen receptor binding of progestagens used in oral contraceptives. Contraception. 1988 Sep;38(3):325-32. [PubMed:3139361]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. List of Drugs Interacting with CYP3A4 - The Cancer Therapy Evaluation Program (CTEP) [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Schurenkamper P, Lisse K: [In-vitro studies on the effect of D-norgestrel and norethisterone acetate on the formation of sex steroids in the human ovary]. Endokrinologie. 1978 Feb;71(1):25-34. [PubMed:639763]

Drug created on November 30, 2015 12:10 / Updated on November 12, 2018 07:36