Norgestrienone

Norgestrienone
Clinical data
Trade namesOgyline, Planor, Miniplanor
Other namesRU-2010; A-301; 17α-Ethynyltrienolone; 17α-Ethynyltrenbolone; Δ9,11-Norethisterone; 17α-Ethynylestra-4,9,11-trien-17β-ol-3-one
Routes of
administration		By mouth
Drug classProgestogen; Progestin; Androgen; Anabolic steroid
ATC code
Identifiers
IUPAC name
  • (8S,13S,14S,17R)-17-ethynyl-17-hydroxy-13-methyl-1,2,6,7,8,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard100.011.544
Edit this at Wikidata
Chemical and physical data
FormulaC20H22O2
Molar mass294.394 g·mol−1
3D model (JSmol)
SMILES
  • O=C4\C=C3/C(=C2/C=C\[C@]1([C@@H](CC[C@]1(C#C)O)[C@@H]2CC3)C)CC4
InChI
  • InChI=1S/C20H22O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,8,10,12,17-18,22H,4-7,9,11H2,2H3/t17-,18+,19+,20+/m1/s1 checkY
  • Key:GVDMJXQHPUYPHP-FYQPLNBISA-N checkY
  (verify)

Norgestrienone, sold under the brand names Ogyline, Planor, and Miniplanor, is a progestin medication which has been used in birth control pills, sometimes in combination with ethinylestradiol.[1][2][3][4][5] It was developed by Roussel Uclaf and has been registered for use only in France.[4][5][6] Under the brand name Planor, it has been marketed in France as 2 mg norgestrienone and 50 μg ethinylestradiol tablets.[7] It is taken by mouth.[5]

Norgestrienone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[8] It has some androgenic activity.[9][10][11][12]

Norgestrienone was first described in the literature in 1965.[10] It is sometimes referred to as a "second-generation" progestin.[13] Norgestrienone is no longer available.[14]

Medical uses

Norgestrienone was used in hormonal contraception to prevent pregnancy.[2][7] It has typically been used as an oral contraceptive at a dosage of 2 mg/day in combination with ethinylestradiol and 350 µ/day when used alone.[5]

Side effects

Pharmacology

Pharmacodynamics

Norgestrienone has been found to possess similar affinity for the progesterone receptor and androgen receptor,[8] and in accordance, has some androgenic activity.[9][10][11][12] The androgenic activity of norgestrienone is greater than that of other 19-nortestosterone derivatives due to the presence of the C9(11) double bond, which enhances said activity.[12] The ratio of progestogenic to androgenic activity appears to be much lower for norgestrienone that it is for other 19-nortestosterone progestins such as norethisterone and levonorgestrel.[15][16][17][18] Gestrinone, the 18-methyl analogue of norgestrienone, has even greater androgenic activity than norgestrienone, as this modification increases androgenic activity similarly.[12]

Relative affinities (%) of norgestrienone and related steroids
CompoundPRARERGRMRSHBGCBG
Norethisterone155–15643–45<0.12.7–2.80.2 ? ?
Norgestrienone63–6570<0.1111.8 ? ?
Levonorgestrel17084–87<0.1140.6–0.9 ? ?
Gestrinone75–7683–85<0.1, 3–10773.2 ? ?
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the PR, testosterone for the AR, E2 for the ER, DEXA for the GR, aldosterone for the MR, DHT for SHBG, and cortisol for CBG. Sources: [15][16][17][18]

Pharmacokinetics

The metabolism of norgestrienone in humans has been studied.[19]

Chemistry

Norgestrienone, also known as 17α-ethynyl-19-nor-δ9,11-testosterone or as 17α-ethynylestra-4,9,11-trien-17β-ol-3-one, as well as δ9,11-norethisterone or 17α-ethynyltrienolone (17α-ethynyltrenbolone), is a synthetic estrane steroid and a derivative of testosterone and 19-nortestosterone.[1][4][20] It is structurally related to the anabolic steroid trenbolone (19-nor-δ9,11-testosterone; the non-17α-ethynylated analogue of norgestrienone), the progestogenic and androgenic steroid gestrinone (the 13β-ethyl variant or 18-methyl derivative of norgestrienone), and the anabolic steroid tetrahydrogestrinone (the 18-methyl and 17α-ethyl variant of norgestrienone).[1][4][21]

History

Norgestrienone was first described in the literature in 1965.[10] It is sometimes referred to as a "second-generation" progestin based on its time of introduction.[13]

Society and culture

Generic names

Norgestrienone is the generic name of the drug and its INN.[1][2][4] It is also known by its developmental code names RU-2010 and A-301.[1][2][4]

Brand names

Norgestrienone has been marketed under the brand names Ogyline, Planor, and Miniplanor.[1][2][4]

Availability

Norgestrienone is no longer marketed and hence is no longer available in any country.[14] It was previously used in France.[14][4] The medication was never marketed in the United States.[22]

Research

Norgestrienone has been studied for use in male hormonal contraception.[23]

References

  1. 1 2 3 4 5 6 Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 887–. ISBN 978-1-4757-2085-3.
  2. 1 2 3 4 5 Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 202–. ISBN 978-94-011-4439-1.
  3. ↑ Diaz S, Pavez M, Quinteros E, Diaz J, Robertson DN, Croxatto HB (October 1978). "Clinical trial with subdermal implants containing norgestrienone". Contraception. 18 (4): 429–40. doi:10.1016/0010-7824(78)90027-6. PMID 720075.
  4. 1 2 3 4 5 6 7 8 Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 751–. ISBN 978-3-88763-075-1.
  5. 1 2 3 4 Sweetman, Sean C., ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2122. ISBN 978-0-85369-840-1. Norgestrienone is a progestogen structurally related to norethisterone that has been used as an oral contraceptive. Typical doses have been 2 mg daily with an oestrogen, and 350 micrograms daily when used alone.
  6. ↑ McGuire JL (2000). Pharmaceuticals, 4 Volume Set. Wiley. p. 1580,1599. ISBN 978-3-527-29874-7.
  7. 1 2 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. 455–. ISBN 978-92-832-1291-1.
  8. 1 2 Loughney DA, Schwender CF (December 1992). "A comparison of progestin and androgen receptor binding using the CoMFA technique". Journal of Computer-Aided Molecular Design. 6 (6): 569–81. doi:10.1007/bf00126215. PMID 1291626. S2CID 22004130.
  9. 1 2 Axelrod J (1 January 1982). Biochemical Actions of Hormones. Academic Press. ISBN 978-0-12-452809-3.
  10. 1 2 3 4 Lauritzen C, Studd JW (22 June 2005). Current Management of the Menopause. CRC Press. pp. 45–. ISBN 978-0-203-48612-2.
  11. 1 2 Di Giulio RT, Monosson E (6 December 2012). Interconnections Between Human and Ecosystem Health. Springer Science & Business Media. pp. 60–. ISBN 978-94-009-1523-7.
  12. 1 2 3 4 Rozenbaum H (March 1982). "Relationships between chemical structure and biological properties of progestogens". Am. J. Obstet. Gynecol. 142 (6 Pt 2): 719–24. doi:10.1016/S0002-9378(16)32477-2. PMID 7065053.
  13. 1 2 Weiss G (February 1999). "Risk of venous thromboembolism with third-generation oral contraceptives: A review". Am. J. Obstet. Gynecol. 180 (2 Pt 2): 295–301. doi:10.1016/S0002-9378(99)70721-0. PMID 9988833.
  14. 1 2 3 http://www.micromedexsolutions.com/micromedex2/%5B%5D
  15. 1 2 Delettré J, Mornon JP, Lepicard G, Ojasoo T, Raynaud JP (January 1980). "Steroid flexibility and receptor specificity". J. Steroid Biochem. 13 (1): 45–59. doi:10.1016/0022-4731(80)90112-0. PMID 7382482.
  16. 1 2 Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, Labrie F, Mornon JP (January 1980). "Steroid hormone receptors and pharmacology". J. Steroid Biochem. 12: 143–57. doi:10.1016/0022-4731(80)90264-2. PMID 7421203.
  17. 1 2 Ojasoo T, Raynaud JP, Doé JC (January 1994). "Affiliations among steroid receptors as revealed by multivariate analysis of steroid binding data". J. Steroid Biochem. Mol. Biol. 48 (1): 31–46. doi:10.1016/0960-0760(94)90248-8. PMID 8136304. S2CID 21336380.
  18. 1 2 Raynaud, J.P.; Ojasoo, T.; Bouton, M.M.; Philibert, D. (1979). "Receptor Binding as a Tool in the Development of New Bioactive Steroids". Drug Design. pp. 169–214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9781483216102.
  19. ↑ Raynaud, J. P. (1971). Metabolism of contraceptive steroids in man. https://www.popline.org/node/480947
  20. ↑ Lavery JP, Sanfilippo JS (6 December 2012). Pediatric and Adolescent Obstetrics and Gynecology. Springer Science & Business Media. pp. 236–. ISBN 978-1-4612-5064-7.
  21. ↑ Gomel V, Brill A (27 September 2010). Reconstructive and Reproductive Surgery in Gynecology. CRC Press. pp. 90–. ISBN 978-1-84184-757-3.
  22. ↑ Daniel Lednicer (4 March 2009). Strategies for Organic Drug Synthesis and Design. John Wiley & Sons. pp. 134–. ISBN 978-0-470-39959-0.
  23. ↑ Scheater, S. B. (1978). The use of progestins and androgens as a male contraceptive. https://www.popline.org/node/443605


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