Aminoglutethimide (Cytadren)

[MaNiCC]

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 and metastatic breast cancer. It is also a drug of abuse by body builders.



Systematic (IUPAC) name
Identifiers
CAS number 125-84-8
ATC code L02BG01
PubChem CID 2145
DrugBank APRD00592
ChemSpider 2060

Chemical data
Formula C13H16N2O2
Mol. mass 232.278 g/mol
SMILES eMolecules & PubChem

Pharmacokinetic data
Bioavailability >95%
Metabolism Hepatic
Half-life 12.5 ± 1.6 hours
Excretion Renal

Therapeutic considerations
Pregnancy cat. D(AU) D(US)
Legal status
Routes Oral
Mechanism
Aminoglutethimide has two mechanisms of action:
1. It blocks aromatase 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. 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.