Chemistry:5α-Dihydrolevonorgestrel

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Short description: Chemical compound
5α-Dihydrolevonorgestrel
5α-Dihydrolevonorgestrel.svg
Clinical data
Other names5α-Dihydrolevonorgestrel; 5α-DHLNG; 5α-LNG
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC21H30O2
Molar mass314.469 g·mol−1
3D model (JSmol)

5α-Dihydrolevonorgestrel (5α-DHLNG) is an active metabolite of the progestin levonorgestrel which is formed by 5α-reductase.[1][2] It has about one-third of the affinity of levonorgestrel for the progesterone receptor.[1] In contrast to levonorgestrel, the compound has both progestogenic and antiprogestogenic activity, and hence has a selective progesterone receptor modulator-like profile of activity.[3][4] This is analogous to the case of norethisterone and 5α-dihydronorethisterone.[3][5] In addition to the progesterone receptor, 5α-DHLNG interacts with the androgen receptor.[6] It has similar affinity for the androgen receptor relative to levonorgestrel (34.3% of that of metribolone for levonorgestrel and 38.0% of that of metribolone for 5α-DHLNG), and has androgenic effects similarly to levonorgestrel and testosterone.[6] 5α-DHLNG is further transformed into 3α,5α- and 3β,5α-THLNG, which bind weakly to the estrogen receptor (0.4 to 2.4% of the RBA of E2) and have weak estrogenic activity.[7][8][4] These metabolites are considered to be responsible for the weak estrogenic activity of high doses of levonorgestrel.[8][4]

v · d · e Relative affinities (%) of levonorgestrel and metabolites
Compound PR AR ER GR MR SHBG CBG
Levonorgestrel 150–162 34a, 45 0 1–8 17–75 50 0
5α-Dihydrolevonorgestrel 50 38a 0 ? ? ? ?
3α,5α-Tetrahydrolevonorgestrel ? ? 0.4 ? ? ? ?
3β,5α-Tetrahydrolevonorgestrel ? ? 2.4 ? ? ? ?
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PR, metribolone (a = mibolerone) for the AR, E2 for the ER, DEXA for the GR, aldosterone for the MR, DHT for SHBG, and cortisol for CBG. Sources: See template.

See also

References

  1. 1.0 1.1 "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric 8 (Suppl 1): 3–63. 2005. doi:10.1080/13697130500148875. PMID 16112947. http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf. 
  2. "Classification and pharmacology of progestins". Maturitas 61 (1–2): 171–80. 2008. doi:10.1016/j.maturitas.2008.11.013. PMID 19434889. 
  3. 3.0 3.1 "Interaction of antiprogestins with progesterone receptors in rat uterus". J. Steroid Biochem. 32 (2): 279–82. February 1989. doi:10.1016/0022-4731(89)90264-1. PMID 2921869. 
  4. 4.0 4.1 4.2 "The intrinsic transcriptional estrogenic activity of a non-phenolic derivative of levonorgestrel is mediated via the estrogen receptor-alpha". J. Steroid Biochem. Mol. Biol. 82 (4–5): 333–41. November 2002. doi:10.1016/s0960-0760(02)00192-9. PMID 12589940. 
  5. "[Antiprogestational action of 5 alpha-dihydronorethisterone]" (in zh). Zhongguo Yao Li Xue Bao 6 (2): 125–9. 1985. PMID 2934946. 
  6. 6.0 6.1 "Molecular interactions of levonorgestrel and its 5 alpha-reduced derivative with androgen receptors in hamster flanking organs". Steroids 60 (9): 630–5. September 1995. doi:10.1016/0039-128X(95)00075-2. PMID 8545853. 
  7. "In vitro metabolism of 17 alpha-ethynylsteroids". J. Steroid Biochem. 10 (4): 437–42. April 1979. doi:10.1016/0022-4731(79)90332-7. PMID 449320. 
  8. 8.0 8.1 "Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites". Eur. J. Pharmacol. 427 (2): 167–74. September 2001. doi:10.1016/S0014-2999(01)01263-8. PMID 11557270.