Aminoglutethimide

Aminoglutethimide

Systematic (IUPAC) name
3-(4-aminophenyl)-3-ethyl-piperidine-2,6-dione
Clinical data
AHFS/Drugs.com	Consumer Drug Information
MedlinePlus	a604039
Pregnancy cat.	D(AU) D(US)
Legal status	?
Routes	Oral
Pharmacokinetic data
Bioavailability	>95%
Metabolism	Hepatic
Half-life	12.5 ± 1.6 hours
Excretion	Renal
Identifiers
CAS number	125-84-8 Y
ATC code	L02BG01
PubChem	CID 2145
DrugBank	APRD00592
ChemSpider	2060 Y
UNII	0O54ZQ14I9 Y
KEGG	D00574 Y
ChEBI	CHEBI:2654 Y
ChEMBL	CHEMBL488 Y
Chemical data
Formula	C13H16N2O2
Mol. mass	232.278 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C13H16N2O2/c1-2-13(8-7-11(16)15-12(13)17)9-3-5-10(14)6-4-9/h3-6H,2,7-8,14H2,1H3,(H,15,16,17) Y Key:ROBVIMPUHSLWNV-UHFFFAOYSA-N Y
N(what is this?)  (verify)

Aminoglutethimide is an anti-steroid drug marketed under the tradename Cytadren by Novartis around the world. It blocks the production of steroids derived from cholesterol and is clinically used in the treatment of Cushing's syndrome^[1] and metastatic breast cancer. It is also used by body builders.

Mechanism

Aminoglutethimide has two mechanisms of action:

1. It blocks aromatase^[2] in the generation of estrogens from androstenedione and testosterone.
2. It blocks the conversion of cholesterol to pregnenolone by inhibiting the enzyme P450scc and consequently decreases synthesis of all hormonally active steroids.

At low doses, aminogluthethimide is only an effective inhibitor of aromatase, but at higher doses, it effectively blocks P450scc as well.

Side effects

Its side effects are skin rash, hepatotoxicity, inhibition of cortisol in the human body, and it may also cause hypothyroidism^{[citation needed]}. Since cortisol helps break down muscle, aminoglutethimide is used by bodybuilders in a steroid cycle.

Clinical uses

Aminoglutethimide is indicated in conjunction with other drugs for the suppression of adrenal function in patients with Cushing's syndrome.

It is also a 2nd or 3rd line choice for the treatment of hormone sensitive (estrogen and progesterone) metastatic breast cancer.

Abuse

Aminoglutethimide is abused by body builders and other steroid users to lower circulating levels of cortisol in the body and prevent muscle loss. Cortisol is catabolic to protein in muscle and effective blockade of P450scc by aminogluthethimide at high doses prevents muscle loss.^{[citation needed]}

References

1. ^ Gross BA, Mindea SA, Pick AJ, Chandler JP, Batjer HH (2007). "Medical management of Cushing disease". Neurosurgical focus 23 (3): E10. doi:10.3171/foc.2007.23.3.12. PMID 17961023. http://thejns.org/doi/abs/10.3171/foc.2007.23.3.12?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov. 
2. ^ Siraki AG, Bonini MG, Jiang J, Ehrenshaft M, Mason RP (July 2007). "Aminoglutethimide-induced protein free radical formation on myeloperoxidase: a potential mechanism of agranulocytosis". Chemical research in toxicology 20 (7): 1038–45. doi:10.1021/tx6003562. PMC 2073000. PMID 17602675. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2073000. 

External links

• Cytadren prescribing information (from the FDA website)
• Medline Plus

See also

• Glutethimide