demegestone

Demegestone has been used to treat luteal insufficiency.{{cite journal | vauthors = Pugeat M, Lejeune H, Dechaud H, Brébant C, Mallein R, Tourniaire J | title = [Luteal insufficiency and elevation of sex-binding proteins by demegestone] | language = fr | journal = Revue Française de Gynécologie et d'Obstétrique | volume = 83 | issue = 7–9 | pages = 495–498 | date = 1988 | pmid = 3194612 }} It has also been studied in combination with estrogens, such as moxestrol, as an oral contraceptive and treatment for infertility.{{cite journal | vauthors = Hamada H, Nagao H, Toyoda H, Hayashi H, Akihiro L, Kotaki S | date = 1970 | title = [Clinical observation on oral contraceptive effect by R-2453 (Abstracts of Papers Presented at Showa 44 in the field of gynecology]). | journal = Japanese Journal of Obstetrics and Gynecology-Acta Obstetrica et Gynaecologica Japonica | volume = 22 | issue = 7 | pages = 753 | url = https://ci.nii.ac.jp/naid/110002126113/ }}{{cite journal | vauthors = Levrier M | date = January 1979 | title = Treatment of Ovarian Sterility with Combined Moxestrol-Demegestone Preparation. | journal = Journal de Gynécologie Obstétrique et Biologie de la Reproduction | volume = 8 | issue = 1 | pages = 89 | location = Paris, France | publisher = Masson Editeur }}

{{See also|Progestin#Side effects}}

Demegestone is a progestogen, and hence is an agonist of the progesterone receptor (PR).{{cite journal| vauthors = Raynaud JP, Cousty C, Salmon J|title=121. Metabolic studies of R2453, a highly potent progestin|journal=Journal of Steroid Biochemistry|volume=5|issue=4|year=1974|pages=324|issn=0022-4731|doi=10.1016/0022-4731(74)90266-0}} It is a highly potent progestogen, showing 50 times the potency of progesterone in the Clauberg test. The ovulation-inbhiting dosage of demegestone is 2.5 mg/day, while the endometrial transformation dosage is 100 mg per cycle.{{cite journal | vauthors = Rabe T, Goeckenjan M, Ahrendt HJ, Crosignani PG, Dinger JC, Mueck AO, Lohr PA, Creinin MD, Sabatini R, Strowitzki T | display-authors = 6 | title = Oral Contraceptive Pills: Combinations, Dosages and the Rationale behind 50 Years or Oral Hormonal Contraceptive Development | journal = Journal für Reproduktionsmedizinund Endokrinologie | date = October 2011 | volume = 8 | issue = 1 | pages = 58–129 | url = http://www.kup.at/kup/pdf/10166.pdf }} The medication is devoid of androgenic activity, and instead has some antiandrogenic activity.{{cite book | vauthors = Raynaud JP, Ojasoo T, Labrie F |title=Mechanisms of Steroid Action|chapter=Steroid hormones—agonists and antagonists|year=1981|pages=145–158|publisher=Macmillan Education UK |doi=10.1007/978-1-349-81345-2_11|isbn=978-1-349-81347-6}} Demegestone has low affinity for the glucocorticoid receptor. In a particular bioassay, both demegestone and progesterone showed antiglucocorticoid rather than glucocorticoid activity.{{cite journal | vauthors = Dausse JP, Duval D, Meyer P, Gaignault JC, Marchandeau C, Raynaud JP | title = The relationship between glucocorticoid structure and effects upon thymocytes | journal = Molecular Pharmacology | volume = 13 | issue = 5 | pages = 948–955 | date = September 1977 | pmid = 895725 }} The major metabolite of demegestone, a 21-hydroxylated metabolite, is a moderately potent progestogen (4 times the potency of progesterone) and a weak mineralocorticoid (2% of the potency of deoxycorticosterone).

Demegestone has good bioavailability. The initial volume of distribution of demegestone is 31 L. Demegestone is metabolized by hydroxylation at the C21, C1, C2, and C11 positions, which is eventually followed by A-ring aromatization after 1,2-dehydration. The major metabolite of demegestone is a 21-hydroxy derivative. The metabolic clearance rate of demegestone is 20 L/h. Its biological half-lives are 2.39 and 0.24 hours with intravenous injection. Demegestone and/or its metabolites are excreted, at least in part, in urine.

{{See also|List of progestogens}}

Demegestone, also known as 17α-methyl-δ⁹-19-norprogesterone or as 17α-methyl-19-norpregna-4,9-diene-3,20-dione, is a synthetic norpregnane steroid and a derivative of progesterone. It is specifically a combined derivative of 17α-methylprogesterone and 19-norprogesterone, or of 17α-methyl-19-norprogesterone. Related derivatives of 17α-methyl-19-norprogesterone include promegestone and trimegestone.

Demegestone was first described in the literature in 1964 and was introduced for medical use in 1974 in France. It was developed by Roussel Uclaf.

Demegestone is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}. It is also known by its developmental code name R-2453 or RU-2453.

Demegestone was marketed under the brand name Lutionex.

Demegestone is no longer marketed and hence is no longer available in any country. It was previously available in France.

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Category:Abandoned drugs

Category:Antiandrogens

Category:Conjugated dienes

Category:Diketones

Category:Enones

Category:Norpregnanes

Category:Progestogens