Anagestone acetate

Anagestone acetate
Clinical data
Trade names Anatropin, Neo-Novum
Routes of
administration		 Oral
Identifiers
Synonyms ORF-1658; Anapregnone acetate; 3-Deketo-6α-methyl-17α-acetoxyprogesterone; 6α-Methyl-17α-hydroxypregn-4-en-20-one acetate
CAS Number 3137-73-3
PubChem (CID) 18443
ChemSpider 221058
Chemical and physical data
Formula C24H36O3
Molar mass 372.54084 g/mol
3D model (Jmol) Interactive image

Anagestone acetate (USAN) (brand name Anatropin; former developmental code name ORF-1658), also known as 3-deketo-6α-methyl-17α-acetoxyprogesterone or as 6α-methyl-17α-acetoxypregn-4-en-20-one, is a steroidal progestin that was formerly marketed by Ortho Pharmaceutical.[1][2] Under the brand name Neo-Novum and in combination with the estrogen mestranol, it was introduced in 1968 as an oral contraceptive,[3][4] but was withdrawn in 1969.[4][5] Anagestone acetate is the acetate ester of anagestone, which, in contrast to anagestone acetate, was never marketed.[1]

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.[4][6][5] In contrast, the non-halogenated 19-nortestosterone derivatives norgestrel, norethisterone, noretynodrel, and etynodiol diacetate were not found to produce such nodules.[5] Because of these findings, anagestone acetate was voluntarily withdrawn from the market by the manufacturer in 1969.[4][5][7] The findings also led to the virtual disappearance of most 17α-hydroxyprogesterone derivatives as hormonal contraceptives from the market (though medroxyprogesterone acetate has continued to be used).[4][6] 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."[5][8] Subsequent research revealed species differences between dogs and humans and established that there is no similar risk in humans.[9]

Mammary tumors in beagle dogs treated by (left) MK-665 (ethynerone with mestranol) and (right) chloroethynyl norgestrel with mestranol for 4 years at a dosage of 1.05 mg/kg/day cyclically.

See also

References

  1. 1 2 J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 85–. ISBN 978-1-4757-2085-3.
  2. ↑ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 322–. ISBN 978-0-8155-1856-3.
  3. ↑ A. Labhart (6 December 2012). Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 571–. ISBN 978-3-642-96158-8.
  4. 1 2 3 4 5 Christian Streffer; H. Bolt; D. Follesdal; P. Hall; J.G. Hengstler; P. Jacob; D Oughton; K. Prieß; E. Rehbinder; E. Swaton (11 November 2013). Low Dose Exposures in the Environment: Dose-Effect Relations and Risk Evaluation. Springer Science & Business Media. pp. 135–. ISBN 978-3-662-08422-9.
  5. 1 2 3 4 5 C.H. Lingeman (6 December 2012). Carcinogenic Hormones. Springer Science & Business Media. pp. 149–. ISBN 978-3-642-81267-5.
  6. 1 2 V. H. T. James; J. R. Pasqualini (22 October 2013). Hormonal Steroids: Proceedings of the Fifth International Congress on Hormonal Steroids. Elsevier Science. pp. 7–. ISBN 978-1-4831-5895-2.
  7. ↑ Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments. United Nations Publications. 1983. pp. 25–. ISBN 978-92-1-130230-1.
  8. ↑ A. Hughes; S. H. Hasan; G. W. Oertel; H. E. Voss; F. Bahner; F. Neumann; H. Steinbeck; K.-J. Gräf; J. Brotherton; H. J. Horn; R. K. Wagner (27 November 2013). Androgens II and Antiandrogens / Androgene II und Antiandrogene. Springer Science & Business Media. pp. 531–. ISBN 978-3-642-80859-3.
  9. ↑ Benno Clemens Runnebaum; Thomas Rabe; Ludwig Kiesel (6 December 2012). Female Contraception: Update and Trends. Springer Science & Business Media. pp. 134–135. ISBN 978-3-642-73790-9.


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