5α-Dihydrolevonorgestrel
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| Other names | 5α-Dihydrolevonorgestrel; 5α-DHLNG; 5α-LNG |
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| Formula | C21H30O2 |
| Molar mass | 314.469 g·mol−1 |
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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 Tooltip estradiol (medication)) 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]
| 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 |
|---|---|---|---|---|---|---|---|
| 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 Tooltip progesterone receptor, metribolone (a = mibolerone) 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: See template. | |||||||
See also
[edit ]References
[edit ]- ^ a b Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.
- ^ Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH (2008). "Classification and pharmacology of progestins". Maturitas. 61 (1–2): 171–80. doi:10.1016/j.maturitas.2008年11月01日3. PMID 19434889.
- ^ a b Vij U, Murugesan K, Kalita JC, Farooq A (February 1989). "Interaction of antiprogestins with progesterone receptors in rat uterus". J. Steroid Biochem. 32 (2): 279–82. doi:10.1016/0022-4731(89)90264-1. PMID 2921869.
- ^ a b c García-Becerra R, Borja-Cacho E, Cooney AJ, Jackson KJ, Lemus AE, Pérez-Palacios G, Larrea F (November 2002). "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. doi:10.1016/s0960-0760(02)00192-9. PMID 12589940. S2CID 24204715.
- ^ Chu YH, Li QA, Zhao ZF, Zhou YP, Cao DC (1985). "[Antiprogestational action of 5 alpha-dihydronorethisterone]". Zhongguo Yao Li Xue Bao (in Chinese). 6 (2): 125–9. PMID 2934946.
- ^ a b Cabeza M, Vilchis F, Lemus AE, Díaz de León L, Pérez-Palacios G (September 1995). "Molecular interactions of levonorgestrel and its 5 alpha-reduced derivative with androgen receptors in hamster flanking organs". Steroids. 60 (9): 630–5. doi:10.1016/0039-128X(95)00075-2. PMID 8545853. S2CID 20869899.
- ^ Khan FS, Fotherby K (April 1979). "In vitro metabolism of 17 alpha-ethynylsteroids". J. Steroid Biochem. 10 (4): 437–42. doi:10.1016/0022-4731(79)90332-7. PMID 449320.
- ^ a b Santillán R, Pérez-Palacios G, Reyes M, Damián-Matsumura P, García GA, Grillasca I, Lemus AE (September 2001). "Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites". Eur. J. Pharmacol. 427 (2): 167–74. doi:10.1016/S0014-2999(01)01263-8. PMID 11557270.
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