MedlinePlus a604039 ATC code L02BG01 (WHO) Molar mass 232.278 g/mol | Routes of
administration Oral Bioavailability >95% CAS ID 125-84-8 | |
 | ||
AHFS/Drugs.com Consumer Drug Information Pregnancy
category AU: D
US: D (Evidence of risk) | ||
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 used by bodybuilders.
Contents
Mechanism
Aminoglutethimide has two mechanisms of action:
- It blocks aromatase in the generation of estrogens from androstenedione and testosterone.
- 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 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.
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.