Delmadinone acetate

Delmadinone acetate (DMA), sold under the brand name Tardak among others, is a progestin and antiandrogen which is used in veterinary medicine to treat androgen-dependent conditions such as benign prostatic hyperplasia.^[1][2][3][4] It must be used with care as it has the potential to cause adrenal insufficiency via inhibition of adrenocorticotropic hormone (ACTH) secretion from the pituitary gland.^[5] DMA is the C17α acetate ester of delmadinone, which, in contrast to DMA, was never marketed for medical use.^[1][2]

Delmadinone acetate

Clinical data
Trade names	Tardak, others
Other names	DMA; RS-1310; 1-Dehydrochlormadinone acetate; 1,6-Didehydro-6-chloro-17α-acetoxyprogesterone; 6-Chloro-17α-hydroxypregna-1,4,6-triene-3,20-dione
Drug class	Progestogen; Progestin; Progestogen ester; Steroidal antiandrogen
ATCvet code	QG03DX91 (WHO)
Identifiers
IUPAC name [(8R,9S,10R,13S,14S,17R)-17-acetyl-6-chloro-10,13-dimethyl-3-oxo-9,11,12,14,15,16-hexahydro-8H-cyclopenta[a]phenanthren-17-yl] acetate
CAS Number	13698-49-2
PubChem CID	10135765
ChemSpider	8311278
UNII	92833M0LD9
ChEMBL	ChEMBL2104598
CompTox Dashboard (EPA)	DTXSID60160018
ECHA InfoCard	100.033.821
Chemical and physical data
Formula	C23H27ClO4
Molar mass	402.92 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C\1\C=C/[C@]4(C(=C/1)C(\Cl)=C/[C@@H]2[C@@H]4CC[C@@]3([C@@](OC(=O)C)(C(=O)C)CC[C@@H]23)C)C
InChI InChI=1S/C23H27ClO4/c1-13(25)23(28-14(2)26)10-7-18-16-12-20(24)19-11-15(27)5-8-21(19,3)17(16)6-9-22(18,23)4/h5,8,11-12,16-18H,6-7,9-10H2,1-4H3/t16-,17+,18+,21-,22+,23+/m1/s1 Key:CGBCCZZJVKUAMX-DFXBJWIESA-N

Uses

Veterinary

DMA is used to treat androgen-dependent conditions in animals.^[6] It is most commonly used to treat benign prostatic hyperplasia.^[6] However, it can also be used to treat hypersexuality in male dogs and cats, perianal gland tumors in dogs, and hormone-driven aggression in dogs.^[6]

Pharmacology

Pharmacodynamics

DMA is a progestogen with antigonadotropic and hence antiandrogenic and antiestrogenic effects. In addition, DMA binds to the androgen receptor, and likely acts as an antagonist of this receptor similarly to related drugs like chlormadinone acetate and osaterone acetate.^[7]

Chemistry

See also: List of progestogens, Progestogen ester, List of progestogen esters, Steroidal antiandrogen, and List of steroidal antiandrogens

DMA, also known as 1-dehydrochlormadinone acetate, as well as 1,6-didehydro-6-chloro-17α-acetoxyprogesterone or '6-chloro-17α-hydroxypregna-1,4,6-triene-3,20-dione, is a synthetic pregnane steroid and a derivative of progesterone.^[1][2][4] It is specifically a derivative of 17α-hydroxyprogesterone with a chlorine atom at the C6 position, a double bond between the C1 and C2 positions, another double bond between the C6 and C7 positions, and an acetate ester at the C17α position.^[1][2] Analogues of DMA include other 17α-hydroxyprogesterone derivatives such as chlormadinone acetate, cyproterone acetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, megestrol acetate, and osaterone acetate.^[1][2]

History

DMA was first described in the literature in 1959 and has been marketed since at least 1972.^[1][8][9] It was marketed by this year in Europe and the United Kingdom under the brand names Tardak and Zenadrex.^[9] It was under development for use in the United States as well but does not seem to have ultimately been marketed in this country.^[9]

Society and culture

Generic names

Delmadinone acetate is the generic name of the drug and its USANTooltip United States Adopted Name and BANMTooltip British Approved Name.^[1][2][3][4] Delmadinone is the INNTooltip International Nonproprietary Name and BANTooltip British Approved Name of the unesterified free alcohol form.^[1][2][3][4]

Brand names

DMA is most commonly sold as Tardak, but has also been marketed under a variety of other brand names including Delmate, Estrex, Tardastren, Tardastrex, Vetadinon, and Zenadrex.^[1][2][4]

Availability

DMA is available in Europe and Oceania.^[2][4] It is specifically marketed in the United Kingdom, France, Belgium, Germany, Austria, Switzerland, the Netherlands, Finland, Australia, and New Zealand.^[2][4]

References

1. Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 354–. ISBN 978-1-4757-2085-3.
2. Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 298. ISBN 978-3-88763-075-1. Retrieved 30 May 2012.
3. Morton I, Hall JM (1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer. p. 92. ISBN 978-0-7514-0499-9. Retrieved 30 May 2012.
4. "List of Progestins". Drugs.com.
5. Court EA, Watson AD, Church DB, Emslie DR (August 1998). "Effects of delmadinone acetate on pituitary-adrenal function, glucose tolerance and growth hormone in male dogs" (PDF). Australian Veterinary Journal. 76 (8): 555–560. doi:10.1111/j.1751-0813.1998.tb10216.x. PMID 9741725.
6. McLauchlan G, Ramsey I (2008). "Update on medical management of benign prostatic hyperplasia". Companion Animal. 13 (7): 39–41. doi:10.1111/j.2044-3862.2008.tb00313.x. ISSN 1464-4630.
7. McRobb L, Handelsman DJ, Kazlauskas R, Wilkinson S, McLeod MD, Heather AK (May 2008). "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. doi:10.1016/j.jsbmb.2007.10.008. PMID 18395441. S2CID 5612000.
8. Ringold HJ, Batres E, Bowers A, Edwards J, Zderic J (1959). "Steroids. Cxxvii.16-Halo Progestational Agents". Journal of the American Chemical Society. 81 (13): 3485–3486. doi:10.1021/ja01522a090. ISSN 0002-7863.
9. Modern Veterinary Practice. Vol. 53. 1972. p. 46. John T. Bryans, University of Kentucky, Lexington. Thoroughbred Record 194(22): 1634-1636, 1971. In the clinical review entitled "Antiandrogen Treatment of Prostate Disorders" (MVP Oct, p 46} the product should have been identified as delta-chlor- madinone acetate (delta-CAP, rather than as CAP). This compound, also known as delmadinone acetate, has unique properties and is marketed in Europe and the UK as Tardak® and Zenadrex®; It is presently subject to clinical investigation in the US for FDA approval.