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Chemical compound
Demegestone
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 administration
By mouth
[1]
Drug class
Progestogen ;
Progestin
ATC code
Bioavailability Good
[2]
Metabolism
Hydroxylation , others
[2]
Metabolites • 21-Hydroxydemegestone
[2] • Others
[2]
Excretion
Urine
[2]
(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
Formula C 21 H 28 O 2
Molar mass 312.453 g·mol−1 3D model (
JSmol )
CC(=O)[C@]1(CC[C@@H]2[C@@]1(CCC3=C4CCC(=O)C=C4CC[C@@H]23)C)C
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 name Lutionex , is a
progestin medication which was previously used to treat
luteal insufficiency but is now no longer marketed.
[3]
[4]
[5]
[6]
[7] It is taken
by mouth .
[2]
[1]
Demegestone is a progestin, or a
synthetic
progestogen , and hence is an
agonist of the
progesterone receptor , the
biological target of progestogens like
progesterone .
[6]
[2]
[8] It has no
androgenic activity.
[2]
Demegestone was first described in 1966 and was introduced for medical use in
France in 1974.
[3]
[4] It has only been marketed in France, and has since been discontinued in this country.
[5]
[4]
Medical uses
Demegestone has been used to treat
luteal insufficiency .
[7] It has also been studied in combination with
estrogens , such as
moxestrol , as an
oral contraceptive and treatment for
infertility .
[1]
[9]
[10]
Side effects
Pharmacology
Pharmacodynamics
Demegestone is a
progestogen , and hence is an
agonist of the
progesterone receptor (PR).
[6]
[8]
[2] It is a highly
potent progestogen, showing 50 times the potency of
progesterone in the
Clauberg test .
[2] The
ovulation -inbhiting dosage of demegestone is 2.5 mg/day, while the
endometrial transformation dosage is 100 mg per cycle.
[11] The medication is devoid of
androgenic activity,
[2] and instead has some
antiandrogenic activity.
[12] Demegestone has low
affinity for the
glucocorticoid receptor .
[13] In a particular
bioassay , both demegestone and progesterone showed
antiglucocorticoid rather than
glucocorticoid activity.
[14] 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 ).
[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 (%). Reference
ligands (100%) were
progesterone for the
PR Tooltip progesterone receptor ,
testosterone 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:
[13]
[15]
[16]
[17]
Pharmacokinetics
Demegestone has good
bioavailability .
[2] The initial
volume of distribution of demegestone is 31 L.
[2] 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 .
[2] The major metabolite of demegestone is a 21-
hydroxy
derivative .
[2] The
metabolic clearance rate of demegestone is 20 L/h.
[2] Its
biological half-lives are 2.39 and 0.24 hours with
intravenous injection .
[2] Demegestone and/or its metabolites are
excreted , at least in part, in
urine .
[2]
Chemistry
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 .
[3]
[4]
[6] It is specifically a combined derivative of
17α-methylprogesterone and
19-norprogesterone , or of
17α-methyl-19-norprogesterone .
[3]
[4]
[6] Related derivatives of 17α-methyl-19-norprogesterone include
promegestone and
trimegestone .
[3]
[6]
History
Demegestone was first described in the literature in 1964 and was introduced for medical use in 1974 in
France .
[3]
[4] It was developed by
Roussel Uclaf .
[4]
Society and culture
Generic names
Demegestone is the
generic name of the drug and its
INN Tooltip International Nonproprietary Name .
[3] It is also known by its developmental code name R-2453 or RU-2453 .
[3]
Brand names
Demegestone was marketed under the brand name Lutionex.
[3]
[4]
Availability
Demegestone is no longer marketed and hence is no longer available in any country.
[5] It was previously available in
France .
[5]
[4]
References
^
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 . Springer. pp. 356–.
ISBN
978-1-4757-2085-3 .
^
a
b
c
d
e
f
g
h
i William Andrew Publishing (22 October 2013).
Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Elsevier. pp. 1215–.
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 . 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 .
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Agonists
SARMs Tooltip Selective androgen receptor modulator Antagonists
GPRC6A
GR Tooltip Glucocorticoid receptor
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SPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
mPR Tooltip Membrane progesterone receptor (
PAQR Tooltip Progestin and adipoQ receptor )