DrugBank: Norgestimate (DB00957)

targets (2) transporters (1)

Identification

Name

Norgestimate

Accession Number

DB00957 (APRD00569)

Type

small molecule

Groups

approved

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Dexnorgestrel Acetime
Norgestimato [INN-Spanish]
Norgestimatum [INN-Latin]

Brand names

Ortho Cyclen-21
Ortho Cyclen-28
Ortho Tri-Cyclen
Ortho-Prefest

Brand name mixtures

Tri-Cyclen Tablets - 21-Day (Ethinyl Estradiol + Norgestimate)
Tri-Cyclen Tablets - 28-Day (Ethinyl Estradiol + Norgestimate)

Categories

Contraceptives
Contraceptives, Oral, Synthetic

CAS number

35189-28-7

Weight

Average: 369.4971
Monoisotopic: 369.230393863

Chemical Formula

C₂₃H₃₁NO₃

InChI Key

InChIKey=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

Plain Text

IUPAC Name

(1S,2R,5E,10R,11S,14R,15S)-15-ethyl-14-ethynyl-5-(hydroxyimino)tetracyclo[8.7.0.0^{2,7}.0^{11,15}]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])CCC(\C=C3CC[C@@]21[H])=N/O

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Not Available

Classes

Steroids and Steroid Derivatives

Substructures

Steroids and Steroid Derivatives
Carboxylic Acids and Derivatives
Hydroxy Compounds
Alkanes and Alkenes
Acetates
Alkynes
Ethers
Imines
Cyclohexenes and Derivatives
Oximes and Derivatives

Pharmacology

Indication

For the prevention of pregnancy

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.

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

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

Form	Route	Strength
Tablet	Oral

Prices

Unit description	Cost	Unit
Ortho Tri-Cyclen Lo 28 0.18/0.215/0.25 mg-25 mcg tablet Disp Pack	78.06 USD	disp
Ortho Tri-Cyclen (28) 28 0.18/0.215/0.25 mg-35 mcg tablet Disp Pack	47.99 USD	disp
Ortho-Cyclen (28) 28 0.25-35 mg-mcg tablet Disp Pack	38.99 USD	disp
Ortho tri-cyclen lo tablet	2.68 USD	tablet
Ortho-prefest tablet	1.36 USD	tablet
Ortho-cyclen 28 tablet	1.13 USD	tablet

Patents

Country	Patent Number	Approved	Expires
United States	7320970	2000-03-30	2020-03-30
United States	5382573	1995-01-17	2012-01-17

Properties

State

solid

Melting point

216 oC

Experimental Properties

Property	Value	Source
logP	4.8	PhysProp

Predicted Properties

Property	Value	Source
water solubility	5.31e-03 g/l	ALOGPS
logP	3.80	ALOGPS
logP	4.03	ChemAxon Molconvert
logS	-4.84	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	3	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	58.89	ChemAxon Molconvert
rotatable bond count	3	ChemAxon Molconvert
refractivity	105.00	ChemAxon Molconvert
polarizability	42.82	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
PubChem Compound	6540478
PubChem Substance	46507381
ChemSpider	5022837
ChEBI	50815
ChEMBL	50815
Therapeutic Targets Database	DAP001210
PharmGKB	PA450655
Drug Product Database	0
RxList	http://www.rxlist.com/cgi/generic/norgestimest.htm
Wikipedia	http://en.wikipedia.org/wiki/Norgestimate

ATC Codes

G03AA11

AHFS Codes

Not Available

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 Gene: PGR Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Graziottin A: A review of transdermal hormonal contraception : focus on the ethinylestradiol/norelgestromin contraceptive patch. Treat Endocrinol. 2006;5(6):359-65. Pubmed 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 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 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 Gene: ESR1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Pasqualini JR: Differential effects of progestins on breast tissue enzymes. Maturitas. 2003 Dec 10;46 Suppl 1:S45-54. Pubmed 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 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

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

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
Graziottin A: A review of transdermal hormonal contraception : focus on the ethinylestradiol/norelgestromin contraceptive patch. Treat Endocrinol. 2006;5(6):359-65. Pubmed
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
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
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:

Pasqualini JR: Differential effects of progestins on breast tissue enzymes. Maturitas. 2003 Dec 10;46 Suppl 1:S45-54. Pubmed
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
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

Transporters
1. Canalicular multispecific organic anion transporter 1 Actions: substrate Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter UniProt ID: Q92887 Gene: ABCC2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Transporters

1. Canalicular multispecific organic anion transporter 1

Actions: substrate

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out

Gene: ABCC2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Comments

Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

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.