Chemical compound
Pharmaceutical compound
Demegestone Clinical data Trade names Lutionex Other names Dimegestone; R-2453; RU-2453; 17α-Methyl-δ9 -19-norprogesterone; 17α-Methyl-19-norpregna-4,9-diene-3,20-dione Routes of By mouth [ 1] Drug class Progestogen ;Progestin ATC code Pharmacokinetic dataBioavailability Good[ 2] Metabolism Hydroxylation , others[ 2] Metabolites • 21-Hydroxydemegestone[ 2] [ 2] Excretion Urine [ 2] Identifiers (8S ,13S ,14S ,17S )-17-acetyl-13,17-dimethyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a ]phenanthren-3-one
CAS Number PubChem CID ChemSpider UNII KEGG ChEBI ChEMBL CompTox Dashboard (EPA) ECHA InfoCard 100.030.278 Chemical and physical data Formula C 21 H 28 O 2 Molar mass −1 3D model (JSmol ) InChI=1S/C21H28O2/c1-13(22)20(2)11-9-19-18-6-4-14-12-15(23)5-7-16(14)17(18)8-10-21(19,20)3/h12,18-19H,4-11H2,1-3H3/t18-,19+,20-,21+/m1/s1
Key:JWAHBTQSSMYISL-MHTWAQMVSA-N
Demegestone , sold under the brand nameLutionex , is aprogestin medication which was previously used to treatluteal insufficiency but is now no longer marketed.[ 3] [ 4] [ 5] [ 6] [ 7] by mouth .[ 2] [ 1]
Demegestone is a progestin, or asynthetic progestogen , and hence is anagonist of theprogesterone receptor , thebiological target of progestogens likeprogesterone .[ 6] [ 2] [ 8] androgenic activity.[ 2]
Demegestone was first described in 1966 and was introduced for medical use inFrance in 1974.[ 3] [ 4] [ 5] [ 4]
Demegestone has been used to treatluteal insufficiency .[ 7] estrogens , such asmoxestrol , as anoral contraceptive and treatment forinfertility .[ 1] [ 9] [ 10]
Demegestone is aprogestogen , and hence is anagonist of theprogesterone receptor (PR).[ 6] [ 8] [ 2] potent progestogen, showing 50 times the potency ofprogesterone in theClauberg test .[ 2] ovulation -inbhiting dosage of demegestone is 2.5 mg/day, while theendometrial transformation dosage is 100 mg per cycle.[ 11] androgenic activity,[ 2] antiandrogenic activity.[ 12] affinity for theglucocorticoid receptor .[ 13] bioassay , both demegestone and progesterone showedantiglucocorticoid rather thanglucocorticoid activity.[ 14] metabolite of demegestone, a 21-hydroxylated metabolite, is a moderately potent progestogen (4 times the potency of progesterone) and a weakmineralocorticoid (2% of the potency ofdeoxycorticosterone ).[ 2]
Relative affinities (%) of demegestone 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 Demegestone 230 1 0 5 1–2 ? ? Notes: Values are percentages (%). Referenceligands (100%) wereprogesterone for thePR Tooltip progesterone receptor ,testosterone for theAR Tooltip androgen receptor ,E2 for theER Tooltip estrogen receptor ,DEXA Tooltip dexamethasone for theGR Tooltip glucocorticoid receptor ,aldosterone for theMR Tooltip mineralocorticoid receptor ,DHT Tooltip dihydrotestosterone forSHBG Tooltip sex hormone-binding globulin , andcortisol forCBG Tooltip Corticosteroid-binding globulin .Sources: [ 13] [ 15] [ 16] [ 17]
Demegestone has goodbioavailability .[ 2] volume of distribution of demegestone is 31 L.[ 2] metabolized byhydroxylation at the C21, C1, C2, and C11 positions, which is eventually followed by A-ringaromatization after 1,2-dehydration .[ 2] hydroxy derivative .[ 2] metabolic clearance rate of demegestone is 20 L/h.[ 2] biological half-lives are 2.39 and 0.24 hours withintravenous injection .[ 2] excreted , at least in part, inurine .[ 2]
Demegestone, also known as 17α-methyl-δ9 -19-norprogesterone or as 17α-methyl-19-norpregna-4,9-diene-3,20-dione, is asynthetic norpregnane steroid and aderivative ofprogesterone .[ 3] [ 4] [ 6] 17α-methylprogesterone and19-norprogesterone , or of17α-methyl-19-norprogesterone .[ 3] [ 4] [ 6] promegestone andtrimegestone .[ 3] [ 6]
Demegestone was first described in the literature in 1964 and was introduced for medical use in 1974 inFrance .[ 3] [ 4] Roussel Uclaf .[ 4]
Society and culture [ edit ] Demegestone is thegeneric name of the drug and itsINN Tooltip International Nonproprietary Name .[ 3] R-2453 orRU-2453 .[ 3]
Demegestone was marketed under the brand name Lutionex.[ 3] [ 4]
Demegestone is no longer marketed and hence is no longer available in any country.[ 5] France .[ 5] [ 4]
^a b c Iizuka R, Hayashi M, Kamouchi Y, Yamanaka K (1971). "Evaluation of a low-dose progestagen as a contraceptive".Nihon Funin Gakkai Zasshi .16 (1):68– 82.PMID 12158578 . ^a b c d e f g h i j k l m n o p q r s Raynaud JP, Cousty C, Salmon J (1974). "121. Metabolic studies of R2453, a highly potent progestin".Journal of Steroid Biochemistry .5 (4): 324.doi :10.1016/0022-4731(74)90266-0 .ISSN 0022-4731 . ^a b c d e f g h i Elks J (14 November 2014).The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies ISBN 978-1-4757-2085-3 ^a b c d e f g h i William Andrew Publishing (22 October 2013).Pharmaceutical Manufacturing Encyclopedia ISBN 978-0-8155-1856-3 ^a b c d "Demegestone" .Micromedex .[permanent dead link ^a b c d e f Kuhl H (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration".Climacteric .8 (Suppl 1):3– 63.doi :10.1080/13697130500148875 .PMID 16112947 .S2CID 24616324 . ^a b Pugeat M, Lejeune H, Dechaud H, Brébant C, Mallein R, Tourniaire J (1988). "[Luteal insufficiency and elevation of sex-binding proteins by demegestone]".Revue Française de Gynécologie et d'Obstétrique (in French).83 (7– 9):495– 498.PMID 3194612 . ^a b Lee DL, Kollman PA, Marsh FJ, Wolff ME (September 1977). "Quantitative relationships between steroid structure and binding to putative progesterone receptors".Journal of Medicinal Chemistry .20 (9):1139– 1146.doi :10.1021/jm00219a006 .PMID 926114 . ^ Hamada H, Nagao H, Toyoda H, Hayashi H, Akihiro L, Kotaki S (1970)."[Clinical observation on oral contraceptive effect by R-2453 (Abstracts of Papers Presented at Showa 44 in the field of gynecology])" .Japanese Journal of Obstetrics and Gynecology-Acta Obstetrica et Gynaecologica Japonica .22 (7): 753. ^ Levrier M (January 1979). "Treatment of Ovarian Sterility with Combined Moxestrol-Demegestone Preparation".Journal de Gynécologie Obstétrique et Biologie de la Reproduction .8 (1). Paris, France: Masson Editeur: 89. ^ Rabe T, Goeckenjan M, Ahrendt HJ, Crosignani PG, Dinger JC, Mueck AO, et al. (October 2011)."Oral Contraceptive Pills: Combinations, Dosages and the Rationale behind 50 Years or Oral Hormonal Contraceptive Development" (PDF) .Journal für Reproduktionsmedizinund Endokrinologie .8 (1):58– 129. ^ Raynaud JP, Ojasoo T, Labrie F (1981). "Steroid hormones—agonists and antagonists".Mechanisms of Steroid Action . Macmillan Education UK. pp. 145– 158.doi :10.1007/978-1-349-81345-2_11 .ISBN 978-1-349-81347-6 ^a b 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 . ^ Dausse JP, Duval D, Meyer P, Gaignault JC, Marchandeau C, Raynaud JP (September 1977). "The relationship between glucocorticoid structure and effects upon thymocytes".Molecular Pharmacology .13 (5):948– 955.PMID 895725 . ^ 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 . ^ 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 . ^ Ojasoo T, Raynaud JP (November 1978). "Unique steroid congeners for receptor studies".Cancer Research .38 (11 Pt 2):4186– 4198.PMID 359134 .
GR Tooltip Glucocorticoid receptor
PR Tooltip Progesterone receptor
Agonists Testosterone derivatives: Progestins:6,6-Difluoronorethisterone 6,6-Difluoronorethisterone acetate 17α-Allyl-19-nortestosterone Allylestrenol Altrenogest Chloroethynylnorgestrel Cingestol Danazol Desogestrel Dienogest Ethinylandrostenediol Ethisterone Ethynerone Etonogestrel Etynodiol Etynodiol diacetate Gestodene Gestrinone Levonorgestrel Levonorgestrel esters (e.g.,levonorgestrel butanoate )Lynestrenol Lynestrenol phenylpropionate Metynodiol Metynodiol diacetate Norelgestromin Norethisterone (norethindrone) Norethisterone esters (e.g.,norethisterone acetate ,norethisterone enanthate )Noretynodrel Norgesterone Norgestimate Norgestrel Norgestrienone Norvinisterone Oxendolone Quingestanol Quingestanol acetate Tibolone Tigestol Tosagestin ; Anabolic–androgenic steroids:11β-Methyl-19-nortestosterone 11β-Methyl-19-nortestosterone dodecylcarbonate 19-Nor-5-androstenediol 19-Nor-5-androstenedione 19-Nordehydroepiandrosterone Bolandiol Bolandiol dipropionate Bolandione Dimethisterone Dienedione Dienolone Dimethandrolone Dimethandrolone buciclate Dimethandrolone dodecylcarbonate Dimethandrolone undecanoate Dimethyldienolone Dimethyltrienolone Ethyldienolone Ethylestrenol (ethylnandrol) Methyldienolone Metribolone (R-1881) Methoxydienone (methoxygonadiene) Mibolerone Nandrolone Nandrolone esters (e.g.,nandrolone decanoate ,nandrolone phenylpropionate )Norethandrolone Normethandrone (methylestrenolone, normethandrolone, normethisterone) RU-2309 Tetrahydrogestrinone Trenbolone (trienolone) Trenbolone esters (e.g.,trenbolone acetate ,trenbolone enanthate )Trendione Trestolone Trestolone acetate MixedSPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
mPR Tooltip Membrane progesterone receptor PAQR Tooltip Progestin and adipoQ receptor )
