Danazol

Structural formula
General
Non-proprietary name	Danazol
other names	Danazolum ( Latin ) ; 17 α -ethynyl-17 β - hydroxyandrost- 4-eno [2,3- d ] isoxazole ( IUPAC ) ;
Molecular formula	C 22 H 27 NO 2
Brief description	white or pale yellow crystalline powder
External identifiers / databases
EC number	241-270-1
ECHA InfoCard	100.037.503
PubChem	28417
ChemSpider	26436
DrugBank	DB01406
Wikidata	Q419652
Drug information
ATC code	G03 XA01
Drug class	Antigonadotropin
Mechanism of action	Inhibition of gonadotropin release
properties
Molar mass	337.46 g · mol -1
Physical state	firmly
Melting point	224.4-226.8 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 312-332-361
	P: 280
Toxicological data	4830 mg kg −1 ( LD 50 , mouse , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Danazol is a derivative of testosterone , as the androgen the Hypophysentätigkeit suppressed, and used to spread the treatment of endometriosis was used. It was patented by Sterling Drug in 1959.

effect

Danazol is a fat-soluble , steroidal derivative of testosterone that reversibly inhibits the release of gonadotropins such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which are produced by the pituitary gland.

As with other androgens, there is also an effect on the telomeres , the ends of the chromosomes . There are indications of an interruption in the mitosis-related reduction in telomere length and even of telomere lengthening under danazol therapy, especially in telomeropathies , hereditary diseases with shortened telomere length due to mutation of individual telomere-associated proteins.

application

Danazol has been used to treat endometriosis since the early 1970s and was approved for this indication in the USA. Danazol causes the uterine lining to develop less and thus reduces the symptoms typical of this clinical picture, such as abdominal pain and irregular bleeding.

Outside of this indication, danazol has been used in the treatment of hereditary angioedema , thrombocytopenic purpura, and fibrotic mastopathy .

In Germany there have no longer been any finished medicinal products containing danazol on the market since 2005, as the manufacturer had waived a subsequent approval due to the unfavorable risk-benefit ratio of the oral dosage form.

Side effects

The side effects are determined by its androgenic properties: By inhibiting the female sex hormones, there is an imbalance in favor of the male. The consequences can be hirsutism , acne, and a deeper voice due to the growth of the larynx, as in a broken voice . While the first two side effects are resolved after stopping the drug, the change in voice can be irreversible.

Trade names

Monopreparations

Danatrol (CH), Danokrin (A)

Individual evidence

↑ ^a ^b ^c ^d Entry on Danazol. In: Römpp Online . Georg Thieme Verlag, accessed on May 2, 2014.
↑ ^a ^b Datasheet Danazol from Sigma-Aldrich , accessed on March 24, 2011 ( PDF ).
↑ Danielle M. Townsley, Bogdan Dumitriu, Delong Liu, Angélique Biancotto, Barbara Weinstein, Christina Chen, Nathan Hardy, Andrew D. Mihalek, Shilpa Lingala, Yun Ju Kim, Jianhua Yao, Elizabeth Jones, Bernadette R. Gochuico, Theo Heller, Colin O. Wu, Rodrigo T. Calado, Phillip Scheinberg, Neal S. Young: Danazol Treatment for Telomere Diseases . New England Journal of Medicine 2016; Volume 374, Issue 20 of March 19, 2016, pages 1922-1931; DOI: 10.1056 / NEJMoa1515319 .

[RÖMPP_Online-1] Entry on Danazol. In: Römpp Online . Georg Thieme Verlag, accessed on May 2, 2014.

[Sigma-2] Datasheet Danazol from Sigma-Aldrich , accessed on March 24, 2011 ( PDF ).

[3] Danielle M. Townsley, Bogdan Dumitriu, Delong Liu, Angélique Biancotto, Barbara Weinstein, Christina Chen, Nathan Hardy, Andrew D. Mihalek, Shilpa Lingala, Yun Ju Kim, Jianhua Yao, Elizabeth Jones, Bernadette R. Gochuico, Theo Heller, Colin O. Wu, Rodrigo T. Calado, Phillip Scheinberg, Neal S. Young: Danazol Treatment for Telomere Diseases . New England Journal of Medicine 2016; Volume 374, Issue 20 of March 19, 2016, pages 1922-1931; DOI: 10.1056 / NEJMoa1515319 .