Trimegestone

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Trimegestone
Trimegestone.svg
Clinical data
Trade names Ondeva, Totelle Sekvens
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 100%[2]
Metabolism Mainly hydroxylation[1]
Biological half-life 13.8 hours[1]
Identifiers
Synonyms RU-27987
CAS Number
PubChem CID
ChemSpider
KEGG
ChEMBL
ECHA InfoCard 100.189.099
Chemical and physical data
Formula C22H30O3
Molar mass 342.472 g/mol
3D model (Jmol)

Trimegestone (INN) (brand names Ondeva, Totelle Sekvens (both in combination with estrogen)) is a steroidal progestin of the 19-norprogesterone group related to promegestone which is marketed in Europe as a hormonal contraceptive and for use in hormonal replacement therapy for postmenopausal symptoms.[3][4][5][6][7]

Pharmacology[edit]

Trimegestone has very high affinity for the progesterone receptor, only weak affinity for the mineralocorticoid receptor, and little or no affinity for other steroid hormone receptors.[4][5][8] In accordance, it is described as a very potent and pure progestogen,[4] in fact the most potent progestin of the 19-norprogesterone group (clinically effective in endometriosis at only 0.1 mg/day),[4][5][1] and possesses weak antimineralocorticoid activity and no androgenic, antiandrogenic, estrogenic, or glucocorticoid activity.[1][9] Unlike progesterone, trimegestone does not metabolize into neurosteroids and hence does not influence GABAA receptor signaling or produce sedative side effects.[9]

Pharmacokinetics[edit]

The oral bioavailability of trimegestone is 100%.[2] Its elimination half-life is 13.8 hours.[1] It is metabolized mainly via hydroxylation.[1]

Chemistry[edit]

Trimegestone is a 19-norpregnane steroid and a derivative of 19-norprogesterone (19-norpregn-4-ene-3,20-dione) and 17α-methylprogesterone. It is also known as 21(S)-hydroxy-17α,21-dimethyl-9-dehydro-19-norprogesterone? or 21(S)-hydroxy-17α,21-dimethyl-19-norpregna-4,9-dien-3,20-dione?, as well as 17β-(S)-lactoyl-17α-methylestra-4,9-dien-3-one or 17β-((S)-2-hydroxypropanoyl)-17α-methylestra-4,9-dien-3-one.

Trimegestone is closely related structurally to the 19-norprogesterone and 17α-methylprogesterone derivatives demegestone and promegestone and is also known as 21-hydroxypromegestone. It is also related to the 19-norprogesterone derivatives gestonorone caproate, nomegestrol acetate, norgestomet, and segesterone acetate and to the 17α-methylprogesterone derivative medrogestone.

History[edit]

Trimegestone was first introduced in 2001.[6][10]

Society and culture[edit]

Brand names[edit]

Trimegestone is marketed in combination with an estrogen under the brand names Ondeva and Totelle Sekvens.[10][7][11]

Availability[edit]

Trimegestone is marketed in France and Sweden and possibly also in other European countries.[7][12] It is not available in the United States.[8]

References[edit]

  1. ^ a b c d e f Kuhl, H (2009). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 (sup1): 3–63. doi:10.1080/13697130500148875. ISSN 1369-7137. PMID 16112947. 
  2. ^ a b Howard J.A. Carp, MB,BS, FRCOG (9 April 2015). Progestogens in Obstetrics and Gynecology. Springer. pp. 38–. ISBN 978-3-319-14385-9. 
  3. ^ C.R. Ganellin; David J. Triggle (21 November 1996). Dictionary of Pharmacological Agents. CRC Press. pp. 2063–. ISBN 978-0-412-46630-4. 
  4. ^ a b c d Eckhard Ottow; Hilmar Weinmann (8 September 2008). Nuclear Receptors as Drug Targets. John Wiley & Sons. pp. 208–. ISBN 978-3-527-62330-3. 
  5. ^ a b c Winnifred Cutler (30 March 2009). Hormones and Your Health: The Smart Woman's Guide to Hormonal and Alternative Therapies for Menopause. John Wiley & Sons. pp. 43–. ISBN 978-0-470-52553-1. 
  6. ^ a b Annual Reports in Medicinal Chemistry. Academic Press. 31 December 2012. pp. 273, 647. ISBN 978-0-12-397214-9. 
  7. ^ a b c Stanczyk FZ (2002). "Pharmacokinetics and potency of progestins used for hormone replacement therapy and contraception". Rev Endocr Metab Disord. 3 (3): 211–24. doi:10.1023/A:1020072325818. PMID 12215716. 
  8. ^ a b Thomas L. Lemke; David A. Williams (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1403–. ISBN 978-1-60913-345-0. 
  9. ^ a b Winneker RC, Bitran D, Zhang Z (2003). "The preclinical biology of a new potent and selective progestin: trimegestone". Steroids. 68 (10-13): 915–20. doi:10.1016/s0039-128x(03)00142-9. PMID 14667983. 
  10. ^ a b John Bodenhan Taylor; D. J. Triggle (2007). Comprehensive Medicinal Chemistry II: Global perspective. Elsevier. ISBN 978-0-08-044514-4. 
  11. ^ Bernardelli, Patrick; Gaudillière, Bernard; Vergne, Fabrice (2002). "Chapter 26. To market, to market - 2001". Annual Reports in Medicinal Chemistry. 37: 257–277. doi:10.1016/S0065-7743(02)37027-1. ISSN 0065-7743. 
  12. ^ Annette M. Doherty (2002). Annual Reports in Medicinal Chemistry. Elsevier. pp. 273–. ISBN 978-0-12-040537-4.