5α-Dihydrolevonorgestrel

5α-Dihydrolevonorgestrel
Clinical data
Other names	5α-Dihydrolevonorgestrel; 5α-DHLNG; 5α-LNG
Identifiers
	IUPAC name (5S,8R,9R,10S,13S,14S,17R)-13-Ethyl-17-ethynyl-17-hydroxy-1,2,4,5,6,7,8,9,10,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-3-one;
CAS Number	78088-19-4;
PubChem CID	9995794;
ChemSpider	8171375;
UNII	7Z4S6960I5;
CompTox Dashboard (EPA)	DTXSID201180481 ;
Chemical and physical data
Formula	C21H30O2
Molar mass	314.469 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CC[C@@H]4[C@@H]3CCC(=O)C4;
	InChI InChI=1S/C21H30O2/c1-3-20-11-9-17-16-8-6-15(22)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,14,16-19,23H,3,5-13H2,1H3/t14-,16-,17+,18+,19-,20-,21-/m0/s1; Key:BMVIRDJAPBCAPQ-WQGSDSCCSA-N;

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 E2Tooltip 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]

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Relative affinities (%) of levonorgestrel and metabolites
Compound	PRTooltip Progesterone receptor	ARTooltip Androgen receptor	ERTooltip Estrogen receptor	GRTooltip Glucocorticoid receptor	MRTooltip Mineralocorticoid receptor	SHBGTooltip Sex hormone-binding globulin	CBGTooltip Corticosteroid binding globulin
Levonorgestrel	150–162	34^a, 45	0	1–8	17–75	50	0
5α-Dihydrolevonorgestrel	50	38^a	0	?	?	?	?
3α,5α-Tetrahydrolevonorgestrel	?	?	0.4	?	?	?	?
3β,5α-Tetrahydrolevonorgestrel	?	?	2.4	?	?	?	?
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PRTooltip progesterone receptor, metribolone (^a = mibolerone) for the ARTooltip androgen receptor, E2 for the ERTooltip estrogen receptor, DEXATooltip dexamethasone for the GRTooltip glucocorticoid receptor, aldosterone for the MRTooltip mineralocorticoid receptor, DHTTooltip dihydrotestosterone for SHBGTooltip sex hormone-binding globulin, and cortisol for CBGTooltip Corticosteroid-binding globulin. Sources: See template.

References

^ ^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.2008.11.013. 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.