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==Abuse== |
==Abuse== |
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Aminoglutethimide is abused by |
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|date=June 2011}} |
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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 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. |
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 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. |
Revision as of 07:31, 21 October 2016
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Clinical data | |
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AHFS/Drugs.com | Consumer Drug Information |
MedlinePlus | a604039 |
Pregnancy category |
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Routes of administration | Oral |
ATC code | |
Pharmacokinetic data | |
Bioavailability | >95% |
Metabolism | Hepatic |
Elimination half-life | 12.5 ± 1.6 hours |
Excretion | Renal |
Identifiers | |
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CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.004.325 |
Chemical and physical data | |
Formula | C13H16N2O2 |
Molar mass | 232.278 g/mol g·mol−1 |
3D model (JSmol) | |
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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
Aminoglutethimide has two mechanisms of action:
- It blocks aromatase[2] 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[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 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]
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 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
References
- ^ 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.
- ^ 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.
External links
- Cytadren prescribing information (from the FDA website)
- Medline Plus