Norgestrienone

Last updated
Norgestrienone
Norgestrienone.svg
Clinical data
Trade names Ogyline, 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 class Progestogen; Progestin; Androgen; Anabolic steroid
ATC code
Identifiers
  • (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 InfoCard 100.011.544 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C20H22O2
Molar mass 294.394 g·mol−1
3D model (JSmol)
  • O=C4\C=C3/C(=C2/C=C\[C@]1([C@@H](CC[C@]1(C#C)O)[C@@H]2CC3)C)CC4
  • 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 Yes check.svgY
  • Key:GVDMJXQHPUYPHP-FYQPLNBISA-N Yes check.svgY
   (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]

Contents

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.[ citation needed ]

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. [14] [15] [16] [17] 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
Compound PR Tooltip Progesterone receptor AR Tooltip Androgen receptor ER Tooltip Estrogen receptor GR Tooltip Glucocorticoid receptor MR Tooltip Mineralocorticoid receptor SHBG Tooltip Sex hormone-binding globulin CBG Tooltip Corticosteroid binding globulin
Norethisterone 155–15643–45<0.12.7–2.80.2 ? ?
Norgestrienone63–6570<0.1111.8 ? ?
Levonorgestrel 17084–87<0.1140.6–0.9 ? ?
Gestrinone 75–7683–85<0.1, 3–10773.2 ? ?
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the PR Tooltip progesterone receptor, testosterone for the AR Tooltip androgen receptor, E2 for the ER Tooltip estrogen receptor, DEXA Tooltip dexamethasone for the GR Tooltip glucocorticoid receptor, aldosterone for the MR Tooltip mineralocorticoid receptor, DHT Tooltip dihydrotestosterone for SHBG Tooltip sex hormone-binding globulin, and cortisol for CBG Tooltip Corticosteroid-binding globulin. Sources: [14] [15] [16] [17]

Pharmacokinetics

The metabolism of norgestrienone in humans has been studied. [18]

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] [19] 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] [20]

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 Tooltip International Nonproprietary Name. [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.[ citation needed ] It was previously used in France. [4] The medication was never marketed in the United States. [21]

Research

Norgestrienone has been studied for use in male hormonal contraception. [22]

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): 429–440. 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 SC, 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): 569–581. Bibcode:1992JCAMD...6..569L. 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". American Journal of Obstetrics and Gynecology. 142 (6 Pt 2): 719–724. 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". American Journal of Obstetrics and Gynecology. 180 (2 Pt 2): 295–301. doi:10.1016/S0002-9378(99)70721-0. PMID   9988833.
  14. 1 2 Delettré J, Mornon JP, Lepicard G, Ojasoo T, Raynaud JP (January 1980). "Steroid flexibility and receptor specificity". Journal of Steroid Biochemistry. 13 (1): 45–59. doi:10.1016/0022-4731(80)90112-0. PMID   7382482.
  15. 1 2 Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, et al. (January 1980). "Steroid hormone receptors and pharmacology". Journal of Steroid Biochemistry. 12: 143–157. doi:10.1016/0022-4731(80)90264-2. PMID   7421203.
  16. 1 2 Ojasoo T, Raynaud JP, Doé JC (January 1994). "Affiliations among steroid receptors as revealed by multivariate analysis of steroid binding data". The Journal of Steroid Biochemistry and Molecular Biology. 48 (1): 31–46. doi:10.1016/0960-0760(94)90248-8. PMID   8136304. S2CID   21336380.
  17. 1 2 Raynaud J, Ojasoo T, Bouton M, Philibert D (1979). "Receptor Binding as a Tool in the Development of New Bioactive Steroids". Drug Design. Medicinal Chemistry: A Series of Monographs. Vol. 11. Academic Press. pp. 169–214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN   9781483216102.
  18. ↑ Raynaud JP (1970). "Metabolism of contraceptive steroids in man". Excerpta Medica International Congress Series. 219: 915–922. Archived from the original on 29 March 2018.
  19. ↑ 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.
  20. ↑ Gomel V, Brill A (27 September 2010). Reconstructive and Reproductive Surgery in Gynecology. CRC Press. pp. 90–. ISBN   978-1-84184-757-3.
  21. ↑ Lednicer D (4 March 2009). Strategies for Organic Drug Synthesis and Design. John Wiley & Sons. pp. 134–. ISBN   978-0-470-39959-0.
  22. ↑ Schearer SD (1978). The use of progestins and androgens as a male contraceptive. Hormonal control of male fertility. DHEW Publication No.(NIH). (Report). pp. 78–1097. Archived from the original on 29 March 2018.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.