Aminoglutethimide

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Aminoglutethimide
Aminoglutethimide.svg
Clinical data
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a604039
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
Routes of
administration
Oral
ATC code
Pharmacokinetic data
Bioavailability >95%
Metabolism Hepatic
Biological half-life 12.5 ± 1.6 hours
Excretion Renal
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.004.325
Chemical and physical data
Formula C13H16N2O2
Molar mass 232.278 g/mol
3D model (JSmol)
  (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 bodybuilders.

Mechanism[edit]

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[edit]

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[edit]

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[edit]

Aminoglutethimide is abused by bodybuilders 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]

Aminoglutethimide has more recently found use as a recreational CYP2D6 inducer, resulting in an increased conversion of codeine to morphine when the former is taken concomitantly with aminoglutethimide. This increases the effect of codeine per dose and increases the ceiling effect threshold, allowing smaller doses of codeine to achieve the same effect as a larger dose taken alone as well as increasing the metabolic limit on the effect of codeine (normally codeine doses above 400 mg stop producing any significant increase in opioid effects due to depletion of the CYP2D6 enzyme which essentially halts the conversion process until the enzyme has replenished). A similar effect is seen with tramadol due to an increased conversion to O-desmethyltramadol and an increased availability of the CYP2D6 enzyme.

See also[edit]

References[edit]

  1. ^ Gross BA, Mindea SA, Pick AJ, Chandler JP, Batjer HH (2007). "Medical management of Cushing disease". Neurosurgical focus. 23 (3): E10. PMID 17961023. doi:10.3171/foc.2007.23.3.12. 
  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. PMC 2073000Freely accessible. PMID 17602675. doi:10.1021/tx6003562. 

External links[edit]