Norgestimate

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Norgestimate
Norgestimate.svg
Clinical data
Trade names Ortho-Cyclen, Ortho Tri-Cyclen, Previfem, Sprintec, Prefest, others
Synonyms ORF-10131; Norgestrel acetate oxime; Norgestrel 17β-acetate 3-oxime; 17α-Ethynyl-18-methyl-19-nortestosterone 3-oxime 17β-acetate; 17α-Ethynyl-18-methylestr-4-en-17β-ol-3-one 3-oxime 17β-acetate
AHFS/Drugs.com Micromedex Detailed Consumer Information
MedlinePlus a601050
Routes of
administration
By mouth
Drug class Progestogen; Progestogen ester
ATC code
Legal status
Legal status
Pharmacokinetic data
Biological half-life 12–30 hours
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
Formula C23H31NO3
Molar mass 369.497 g/mol
3D model (JSmol)
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Norgestimate, sold under the brand names Ortho-Cyclen, Ortho Tri-Cyclen, Previfem, Sprintec, and Prefest among others, is a progestin that is used in combination with ethinylestradiol as an oral contraceptive and in combination with estradiol in menopausal hormone replacement therapy.[1] It is a prodrug, mainly of norelgestromin, but also of levonorgestrel in small amounts.[1][2]

Pharmacology[edit]

Pharmacodynamics[edit]

Norgestimate, unlike related progestins such as levonorgestrel, shows high selectivity for the progesterone receptor (PR) and little androgenic activity.[1][3] Moreover, norgestimate and its main active metabolite norelgestromin do not bind to or occupy sex hormone-binding globulin (SHBG).[1] In accordance, clinical trials of norgestimate have observed minimal androgenic side effects.[3]

Androgenic activity[edit]

The relative binding affinity of norgestimate and its metabolite norelgestromin for the rat prostatic androgen receptor (AR) are 0.3% and 1.3% of those of dihydrotestosterone (DHT), respectively, whereas the respective values for levonorgestrel and gestodene are 22.0% and 15.4%.[4] Moreover, the ratios of AR to PR binding are 219 for norgestimate and 48 for its metabolite norelgestromin, whereas the ratios of progesterone, levonorgestrel, and gestodene are 93, 11, and 28, respectively.[4]

Estrogens increase and androgens inhibit hepatic production of SHBG and by extension circulating SHBG levels.[4] Clinical studies have found that norgestimate does not appreciably inhibit the increase in SHBG levels produced by ethinylestradiol, and this is in accordance with preclinical research and the notion that norgestimate is minimally androgenic.[4] In addition, norgestimate and norelgestromin show virtually no affinity for SHBG, unlike levonorgestrel and gestodene (which have 87% and 202% of the relative binding affinity of testosterone for SHBG, respectively) but similarly to progesterone.[4]

Pharmacokinetics[edit]

Norgestimate acts as a prodrug to norelgestromin (17β-deacetylnorgestimate or levonorgestrel 3-oxime), the primary active metabolite, and to a lesser extent to levonorgestrel (~22% of an administered dose; deacetylation of norgestimate occurs in the intestines and the liver), as well as to levonorgestrel 17β-acetate in very small quantities.[1][5][6]

Chemistry[edit]

Norgestimate, also known as 17α-ethynyl-18-methyl-19-nortestosterone 3-oxime 17β-acetate or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one 3-oxime 17β-acetate, is a synthetic estrane steroid and a derivative of testosterone.[7][8] It is more specifically a derivative of norethisterone (17α-ethynyl-19-nortestosterone) and is a member of the gonane (18-methylestrane) subgroup of the 19-nortestosterone family of progestins.[9] Norgestimate is the C3 oxime and C17β acetate ester of levonorgestrel and is also known as levonorgestrel acetate oxime.[10]

History[edit]

Norgestimate was introduced in 1986.[11]

Society and culture[edit]

Generic names[edit]

Norgestimate is the generic name of the drug and its INN, USAN, USP, BAN, and DCF.[7][8]

See also[edit]

References[edit]

  1. ^ a b c d e Thomas L. Lemke; David A. Williams (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1316–. ISBN 978-0-7817-6879-5. 
  2. ^ Tommaso Falcone; William W. Hurd (2007). Clinical Reproductive Medicine and Surgery. Elsevier Health Sciences. pp. 389–. ISBN 0-323-03309-1. 
  3. ^ a b Chapdelaine A, Desmarais JL, Derman RJ (1989). "Clinical evidence of the minimal androgenic activity of norgestimate". Int. J. Fertil. 34 (5): 347–52. PMID 2571595. 
  4. ^ a b c d e Phillips A, Hahn DW, McGuire JL (1992). "Preclinical evaluation of norgestimate, a progestin with minimal androgenic activity". Am. J. Obstet. Gynecol. 167 (4 Pt 2): 1191–6. PMID 1415445. 
  5. ^ IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; World Health Organization; International Agency for Research on Cancer (2007). Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. World Health Organization. pp. 150–151. ISBN 978-92-832-1291-1. 
  6. ^ Stanczyk FZ (2002). "Pharmacokinetics and potency of progestins used for hormone replacement therapy and contraception". Rev Endocr Metab Disord. 3 (3): 211–24. doi:10.1023/A:1020072325818. PMID 12215716. 
  7. ^ a b J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 887–. ISBN 978-1-4757-2085-3. 
  8. ^ a b https://www.drugs.com/international/norgestimate.html
  9. ^ Jerome Frank Strauss; Robert L. Barbieri (2009). Yen and Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. Elsevier Health Sciences. pp. 878–. ISBN 1-4160-4907-X. 
  10. ^ Sven O. Skouby (15 July 1997). Clinical Perspectives on a New Gestodene Oral Contraceptive Containing 20μg of Ethinylestradiol. CRC Press. pp. 11–. ISBN 978-1-85070-786-8. 
  11. ^ Benno Clemens Runnebaum; Thomas Rabe; Ludwig Kiesel (6 December 2012). Female Contraception: Update and Trends. Springer Science & Business Media. pp. 13–. ISBN 978-3-642-73790-9.