Identification

Name
Norgestimate
Accession Number
DB00957  (APRD00569)
Type
Small Molecule
Groups
Approved, Investigational
Description

Norgestimate is a form of progesterone, which is a female hormone important for the regulation of ovulation and menstruation. Norgestimate is used with estradiol to treat the symptoms of menopause.

Structure
Thumb
Synonyms
  • (+)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one oxime acetate (ester)
  • (17α)-17-(Acetyloxy)-13-ethyl-18,19-dinorpregn-4-en-20-yn-3-one 3-oxime
  • d-13β-Ethyl-17α-ethynyl-17β-acetoxygon-4-en-3-one oxime
  • Dexnorgestrel Acetime
  • Norgestimate
  • Norgestimato
  • Norgestimatum
External IDs
ORF 10131 / RWJ 10131
Active Moieties
NameKindUNIICASInChI Key
NorelgestrominprodrugR0TAY3X63153016-31-2ISHXLNHNDMZNMC-XUDSTZEESA-N
Product Images
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Centrisa 21Norgestimate (0.180 mg) + Norgestimate (0.215 mg) + Norgestimate (0.250 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg)TabletOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Centrisa 21Norgestimate (0.180 mg) + Norgestimate (0.215 mg) + Norgestimate (0.250 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg)TabletOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Centrisa 21Norgestimate (0.180 mg) + Norgestimate (0.215 mg) + Norgestimate (0.250 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg)TabletOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Centrisa 28Norgestimate (0.180 mg) + Norgestimate (0.215 mg) + Norgestimate (0.250 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg)TabletOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Centrisa 28Norgestimate (0.180 mg) + Norgestimate (0.215 mg) + Norgestimate (0.250 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg)TabletOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Centrisa 28Norgestimate (0.180 mg) + Norgestimate (0.215 mg) + Norgestimate (0.250 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg) + Ethinylestradiol (0.035 mg)TabletOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Centrisa Lo 21Norgestimate (0.180 mg) + Norgestimate (0.215 mg) + Norgestimate (0.250 mg) + Ethinylestradiol (0.025 mg) + Ethinylestradiol (0.025 mg) + Ethinylestradiol (0.025 mg)TabletOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Centrisa Lo 21Norgestimate (0.180 mg) + Norgestimate (0.215 mg) + Norgestimate (0.250 mg) + Ethinylestradiol (0.025 mg) + Ethinylestradiol (0.025 mg) + Ethinylestradiol (0.025 mg)TabletOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Centrisa Lo 21Norgestimate (0.180 mg) + Norgestimate (0.215 mg) + Norgestimate (0.250 mg) + Ethinylestradiol (0.025 mg) + Ethinylestradiol (0.025 mg) + Ethinylestradiol (0.025 mg)TabletOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Centrisa Lo 28Norgestimate (0.180 mg) + Norgestimate (0.215 mg) + Norgestimate (0.250 mg) + Ethinylestradiol (0.025 mg) + Ethinylestradiol (0.025 mg) + Ethinylestradiol (0.025 mg)TabletOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
International/Other Brands
Ortho-Prefest
Categories
UNII
C291HFX4DY
CAS number
35189-28-7
Weight
Average: 369.4971
Monoisotopic: 369.230393863
Chemical Formula
C23H31NO3
InChI Key
KIQQMECNKUGGKA-NMYWJIRASA-N
InChI
InChI=1S/C23H31NO3/c1-4-22-12-10-19-18-9-7-17(24-26)14-16(18)6-8-20(19)21(22)11-13-23(22,5-2)27-15(3)25/h2,14,18-21,26H,4,6-13H2,1,3H3/b24-17+/t18-,19+,20+,21-,22-,23-/m0/s1
IUPAC Name
(1S,2R,5E,10R,11S,14R,15S)-15-ethyl-14-ethynyl-5-(hydroxyimino)tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-14-yl acetate
SMILES
[H][C@@]12CC[C@@](OC(C)=O)(C#C)[C@@]1(CC)CC[C@]1([H])[C@@]3([H])CC\C(C=C3CC[C@@]21[H])=N/O

Pharmacology

Indication

For the prevention of pregnancy

Associated Conditions
Associated Therapies
Pharmacodynamics

Norgestimate is used as a female contraceptive. Norgestimate 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. Norgestimate 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

Norgestimate binds to androgen and progestogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like Norgestimate will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.

TargetActionsOrganism
AProgesterone receptor
agonist
Human
AEstrogen receptor alpha
agonist
Human
UAndrogen receptor
partial agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

GI tract/Hepatic

Route of elimination
Not Available
Half life

12-30 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinNorgestimate may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinNorgestimate may decrease the anticoagulant activities of (S)-Warfarin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Norgestimate.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Norgestimate.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Norgestimate.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Norgestimate.
6-Deoxyerythronolide BThe metabolism of Norgestimate can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Norgestimate.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be increased when combined with Norgestimate.
AbataceptThe metabolism of Norgestimate can be increased when combined with Abatacept.
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.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015092
KEGG Drug
D05209
PubChem Compound
6540478
PubChem Substance
46507381
ChemSpider
5022837
ChEBI
50815
ChEMBL
CHEMBL1200934
Therapeutic Targets Database
DAP001210
PharmGKB
PA164744346
RxList
RxList Drug Page
Wikipedia
Norgestimate
ATC Codes
G03AA11 — Norgestimate and ethinylestradiolG03FA13 — Norgestimate and estrogen

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableChronic Hepatitis C Virus (HCV) Infection1
1CompletedNot AvailableHealthy Volunteers1
1CompletedNot AvailableHepatitis C Virus (HCV) Infection1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections2
1CompletedNot AvailablePharmacokinetics1
1CompletedBasic ScienceHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1TerminatedNot AvailableCystic Fibrosis Exacerbations While on and Off Hormonal Contraception1
3CompletedTreatmentContraception1
3RecruitingTreatmentPrimary Ovarian Insufficiency1
4CompletedPreventionBMI >30 kg/m2 / Cardiovascular Disease (CVD) / Insulin Resistance / Metabolic Syndromes1
4CompletedScreeningCardiovascular Risks / Insulin Sensitivity / Perimenopausal Disorder1
Not AvailableCompletedTreatmentThrombosis, Venous1
Not AvailableTerminatedBasic ScienceContraception1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Barr Pharmaceuticals
  • Dept Health Central Pharmacy
  • Dispensing Solutions
  • Duramed
  • Fielding Pharmaceutical Co.
  • Innovative Manufacturing and Distribution Services Inc.
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral
KitOral
Kit
Prices
Unit descriptionCostUnit
Ortho Tri-Cyclen Lo 28 0.18/0.215/0.25 mg-25 mcg tablet Disp Pack78.06USD disp
Ortho Tri-Cyclen (28) 28 0.18/0.215/0.25 mg-35 mcg tablet Disp Pack47.99USD disp
Ortho-Cyclen (28) 28 0.25-35 mg-mcg tablet Disp Pack38.99USD disp
Ortho tri-cyclen lo tablet2.68USD tablet
Ortho-prefest tablet1.36USD tablet
Ortho-cyclen 28 tablet1.13USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5382573No1995-01-172012-01-17Us
US6747019No2004-06-082020-03-20Us
US7320970No2008-01-222020-03-30Us
US6214815Yes2001-04-102019-12-09Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)216 °CPhysProp
logP4.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00531 mg/mLALOGPS
logP3.8ALOGPS
logP4.11ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)11.47ChemAxon
pKa (Strongest Basic)3.11ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area58.89 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity105 m3·mol-1ChemAxon
Polarizability42.82 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9896
Blood Brain Barrier+0.9307
Caco-2 permeable-0.5125
P-glycoprotein substrateSubstrate0.5877
P-glycoprotein inhibitor IInhibitor0.6103
P-glycoprotein inhibitor IINon-inhibitor0.7485
Renal organic cation transporterNon-inhibitor0.6733
CYP450 2C9 substrateNon-substrate0.7842
CYP450 2D6 substrateNon-substrate0.8374
CYP450 3A4 substrateSubstrate0.736
CYP450 1A2 substrateNon-inhibitor0.7596
CYP450 2C9 inhibitorNon-inhibitor0.6541
CYP450 2D6 inhibitorNon-inhibitor0.8829
CYP450 2C19 inhibitorNon-inhibitor0.6215
CYP450 3A4 inhibitorNon-inhibitor0.7716
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7175
Ames testNon AMES toxic0.5404
CarcinogenicityNon-carcinogens0.8389
BiodegradationNot ready biodegradable0.9929
Rat acute toxicity2.4561 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9075
hERG inhibition (predictor II)Non-inhibitor0.7999
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as steroid esters. These are compounds containing a steroid moiety which bears a carboxylic acid ester group.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid esters
Direct Parent
Steroid esters
Alternative Parents
Estrane steroids / Delta-4-steroids / Ynones / Ketoximes / Carboxylic acid esters / Monocarboxylic acids and derivatives / Acetylides / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Steroid ester / Estrane-skeleton / Delta-4-steroid / Ynone / Ketoxime / Carboxylic acid ester / Carboxylic acid derivative / Monocarboxylic acid or derivatives / Oxime / Acetylide
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
terminal acetylenic compound, steroid ester, ketoxime (CHEBI:50815)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. London RS, Chapdelaine A, Upmalis D, Olson W, Smith J: Comparative contraceptive efficacy and mechanism of action of the norgestimate-containing triphasic oral contraceptive. Acta Obstet Gynecol Scand Suppl. 1992;156:9-14. [PubMed:1324557]
  2. Graziottin A: A review of transdermal hormonal contraception : focus on the ethinylestradiol/norelgestromin contraceptive patch. Treat Endocrinol. 2006;5(6):359-65. [PubMed:17107221]
  3. Kuhnz W, Fritzemeier KH, Hegele-Hartung C, Krattenmacher R: Comparative progestational activity of norgestimate, levonorgestrel-oxime and levonorgestrel in the rat and binding of these compounds to the progesterone receptor. Contraception. 1995 Feb;51(2):131-9. [PubMed:7750291]
  4. Juchem M, Pollow K, Elger W, Hoffmann G, Mobus V: Receptor binding of norgestimate--a new orally active synthetic progestational compound. Contraception. 1993 Mar;47(3):283-94. [PubMed:8384965]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
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 tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Pasqualini JR: Differential effects of progestins on breast tissue enzymes. Maturitas. 2003 Dec 10;46 Suppl 1:S45-54. [PubMed:14670645]
  2. Juchem M, Pollow K: Binding of oral contraceptive progestogens to serum proteins and cytoplasmic receptor. Am J Obstet Gynecol. 1990 Dec;163(6 Pt 2):2171-83. [PubMed:2175153]
  3. Shields-Botella J, Duc I, Duranti E, Puccio F, Bonnet P, Delansorne R, Paris J: An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells. J Steroid Biochem Mol Biol. 2003 Nov;87(2-3):111-22. [PubMed:14672731]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Partial 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. Paris F, Rabeolina F, Balaguer P, Bacquet A, Sultan C: Antiandrogenic activity of norgestimate in a human androgen-dependent stable-transfected cell line. Gynecol Endocrinol. 2007 Apr;23(4):193-7. [PubMed:17505938]
  2. Prifti S, Lelle I, Strowitzki T, Rabe T: Induction of androgen receptor activity by norgestimate and norelgestromin in MDA-MB 231 breast cancer cells. Gynecol Endocrinol. 2004 Jul;19(1):18-21. [PubMed:15625768]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
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. Ahire D, Sinha S, Brock B, Iyer R, Mandlekar S, Subramanian M: Metabolite Identification, Reaction Phenotyping, and Retrospective Drug-Drug Interaction Predictions of 17-Deacetylnorgestimate, the Active Component of the Oral Contraceptive Norgestimate. Drug Metab Dispos. 2017 Jun;45(6):676-685. doi: 10.1124/dmd.116.073940. Epub 2017 Mar 10. [PubMed:28283499]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Lindenmaier H, Becker M, Haefeli WE, Weiss J: Interaction of progestins with the human multidrug resistance-associated protein 2 (MRP2). Drug Metab Dispos. 2005 Nov;33(11):1576-9. Epub 2005 Jul 27. [PubMed:16049127]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 17:08