Aminoglutethimide

Aminoglutethimide

Aminoglutethimide
Systematic (IUPAC) name
(RS)-3-(4-aminophenyl)-3-ethyl-piperidine-2,6-dione
Clinical data
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
Routes of
administration
Oral
Pharmacokinetic data
Bioavailability >95%
Metabolism Hepatic
Biological half-life 12.5 ± 1.6 hours
Excretion Renal
Identifiers
CAS Registry Number  Y
ATC code L02
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C13H16N2O2
Molecular mass 232.278 g/mol
 Y   

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.

Contents

  • Mechanism 1
  • Side effects 2
  • Clinical uses 3
  • Abuse 4
  • See also 5
  • References 6
  • External links 7

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. 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.

Aminoglutethamide has more recently found use as a recreational CYP2D6 inducer, resulting in an increased conversion of codeine to morphine when it is taken concomitantly with aminoglutethamide. 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 400mg 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

References

  1. ^ Gross BA, Mindea SA, Pick AJ, Chandler JP, Batjer HH (2007). "Medical management of Cushing disease". Neurosurgical focus 23 (3): E10.  
  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".  

External links

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