Anagestone acetate explained

Anagestone acetate, sold under the brand names Anatropin and Neo-Novum, is a progestin medication which was withdrawn from medical use due to carcinogenicity observed in animal studies.[1] [2] [3]

Medical uses

Anagestone acetate was used in combination with the estrogen mestranol as a combined birth control pill.

Pharmacology

Based on its chemical structure, namely the lack of a C3 ketone, it is probable that anagestone acetate is a prodrug of medroxyprogesterone acetate (the 3-keto analogue).[4] [5]

Chemistry

See also: List of progestogens, Progestogen ester and List of progestogen esters.

Anagestone acetate, also known as 3-deketo-6α-methyl-17α-acetoxyprogesterone or as 6α-methyl-17α-acetoxypregn-4-en-20-one, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone. It is the C17α acetate ester of anagestone, which, in contrast to anagestone acetate, was never marketed. Anagestone acetate is closely related structurally to medroxyprogesterone acetate (6α-methyl-17α-acetoxyprogesterone).

History

Anagestone acetate was introduced in combination with mestranol as a birth control pill in 1968 by Ortho Pharmaceutical.[6] [7] It was withdrawn in 1969.

In 1969, along with a variety of other progestogens including progesterone, chlormadinone acetate, megestrol acetate, medroxyprogesterone acetate, ethynerone, and chloroethynyl norgestrel, anagestone acetate was found to induce the development of mammary gland tumors in Beagle dogs after extensive treatment (2–7 years) with very high doses (10–25 times the recommended human dose), though notably not with 1–2 times the human dosage.[8] [9] In contrast, the non-halogenated 19-nortestosterone derivatives norgestrel, norethisterone, noretynodrel, and etynodiol diacetate were not found to produce such nodules. Because of these findings, anagestone acetate was voluntarily withdrawn from the market by the manufacturer in 1969.[10] The findings also led to the virtual disappearance of most 17α-hydroxyprogesterone derivatives as hormonal contraceptives from the market (though medroxyprogesterone acetate, cyproterone acetate, and chlormadinone acetate have continued to be used). According to Hughes et al., "It is still doubtful how much relevance these findings have for humans as the dog mammary gland seems to be the only one which can be directly maintained by progestogens."[11] Subsequent research revealed species differences between dogs and humans and established that there is no similar risk in humans.[12]

Society and culture

Generic names

Anagestone acetate is the generic name of the drug and its . It is also known by its developmental code name ORF-1658.

Brand names

Anagestone acetate was marketed under the brand names Anatropin and Neo-Novum, the latter in combination with the estrogen mestranol.

Availability

Anagestone acetate was withdrawn from the market and is no longer available.

See also

Notes and References

  1. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 85–.
  2. Book: William Andrew Publishing. Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. 22 October 2013. Elsevier. 978-0-8155-1856-3. 322–.
  3. Book: IARC Working Group on the Evaluation of Carcinogenic Risks to Humans . IV. OESTROGEN-PROGESTIN COMBINATIONS . International Agency for Research on Cancer . 24 June 2022 . en . 1987.
  4. Book: Fraser IS . Estrogens and Progestogens in Clinical Practice. 1998. Churchill Livingstone. 978-0-443-04706-0. 281. Progestational activity depends on the presence of a 3-keto group in ring A of the steroid skeleton. Most of the progestogens used today do indeed carry such a group in their original molecules. However, the 3-keto group is initially missing in the case of desogestrel and norgestimate. They are prodrugs which undergo metabolic conversion to active 3-keto derivatives in the body..
  5. McRobb L, Handelsman DJ, Kazlauskas R, Wilkinson S, McLeod MD, Heather AK . Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay . The Journal of Steroid Biochemistry and Molecular Biology . 110 . 1–2 . 39–47 . May 2008 . 18395441 . 10.1016/j.jsbmb.2007.10.008 . Prodrugs (lack 3-keto): Ethylestrenol, Lynestrenol, Ethynodiol, Allylestrenol, Norgestimate . 5612000 .
  6. Book: Schreiner WE . The Ovary . Labhart A . Clinical Endocrinology: Theory and Practice. https://books.google.com/books?id=DAgJCAAAQBAJ&pg=PA571. 6 December 2012. Springer Science & Business Media. 978-3-642-96158-8. 571–.
  7. Book: Streffer C, Bolt H, Follesdal D, Hall P, Hengstler JG, Jacob P, Oughton D, Prieß K, Rehbinder E, Swaton E . 6 . Interspecies Extrapolation . Low Dose Exposures in the Environment: Dose-Effect Relations and Risk Evaluation. https://books.google.com/books?id=eiL4CAAAQBAJ&pg=PA135. 11 November 2013. Springer Science & Business Media. 978-3-662-08422-9. 135–.
  8. Diczfalusy E . Gregory Pincus and steroidal contraception: a new departure in the history of mankind . Journal of Steroid Biochemistry . 11 . 1A . 3–11 . July 1979 . 385985 . 10.1016/0022-4731(79)90271-1 .
  9. Book: Casey HW, Giles RC, Kwapien RP . Mammary Neoplasia in Animals: Pathologic Aspects and the Effects of Contraceptive Steroids . Carcinogenic Hormones . Recent Results in Cancer Research. Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer . 66 . 129–160 (149) . 1979 . 107546 . 10.1007/978-3-642-81267-5_4 . 978-3-540-08995-7 .
  10. Book: Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments. 1983. United Nations Publications. 978-92-1-130230-1. 25–.
  11. Book: Gräf KJ, Brotherton J, Neumann F . The Clinical Uses of Antiandrogens . Hughes A, Hasan SH, Oertel GW, Voss HE, Bahner F, Neumann F, Steinbeck H, Gräf KJ, Brotherton J, Horn HJ, Wagner RK . 6 . Androgens II and Antiandrogens / Androgene II und Antiandrogene. https://books.google.com/books?id=7JPsCAAAQBAJ&pg=PA531. 27 November 2013. Springer Science & Business Media. 978-3-642-80859-3. 531–.
  12. Book: Runnebaum BC, Rabe T, Kiesel L . Development of Progestogens . Female Contraception: Update and Trends. https://books.google.com/books?id=LtT6CAAAQBAJ&pg=PA134. 6 December 2012. Springer Science & Business Media. 978-3-642-73790-9. 134–135.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Anagestone acetate".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.