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| IUPAC_name = (''RS'')-3-(4-aminophenyl)-3-ethyl-piperidine-2,6-dione |
| IUPAC_name = (''RS'')-3-(4-aminophenyl)-3-ethyl-piperidine-2,6-dione |
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| image = Aminoglutethimide.svg |
| image = Aminoglutethimide.svg |
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| width = |
| width = 175px |
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<!--Clinical data--> |
<!--Clinical data--> |
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| tradename = |
| tradename = Cytadren, others |
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| Drugs.com = {{drugs.com|CDI|aminoglutethimide}} |
| Drugs.com = {{drugs.com|CDI|aminoglutethimide}} |
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| MedlinePlus = a604039 |
| MedlinePlus = a604039 |
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| pregnancy_AU = D |
| pregnancy_AU = D |
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| pregnancy_US = D |
| pregnancy_US = D |
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| routes_of_administration = [[ |
| routes_of_administration = [[Oral administration|By mouth]] |
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| class = [[Aromatase inhibitor]]; [[Antiestrogen]]; [[Steroidogenesis inhibitor]]; [[Antiglucocorticoid]] |
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<!--Pharmacokinetic data--> |
<!--Pharmacokinetic data--> |
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| bioavailability = >95% |
| bioavailability = >95% |
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| protein_bound = |
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| metabolism = [[Liver |
| metabolism = [[Liver]] |
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| elimination_half-life = 12.5 ± 1.6 hours |
| elimination_half-life = 12.5 ± 1.6 hours |
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| excretion = [[ |
| excretion = [[Urine]] |
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<!--Identifiers--> |
<!--Identifiers--> |
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| IUPHAR_ligand = 7054 |
| IUPHAR_ligand = 7054 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 488 |
| ChEMBL = 488 |
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<!--Chemical data--> |
<!--Chemical data--> |
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| C=13 | H=16 | N=2 | O=2 |
| C=13 | H=16 | N=2 | O=2 |
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| molecular_weight = 232.278 g/mol |
| molecular_weight = 232.278 g/mol |
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| |
| SMILES = O=C1NC(=O)CCC1(c2ccc(N)cc2)CC |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C13H16N2O2/c1-2-13(8-7-11(16)15-12(13)17)9-3-5-10(14)6-4-9/h3-6H,2,7-8,14H2,1H3,(H,15,16,17) |
| StdInChI = 1S/C13H16N2O2/c1-2-13(8-7-11(16)15-12(13)17)9-3-5-10(14)6-4-9/h3-6H,2,7-8,14H2,1H3,(H,15,16,17) |
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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]]<ref name="pmid17961023">{{cite journal |vauthors =Gross BA, Mindea SA, Pick AJ, Chandler JP, Batjer HH |title=Medical management of Cushing disease |journal=Neurosurgical focus |volume=23 |issue=3 |pages=E10 |year=2007 |pmid=17961023 |doi=10.3171/foc.2007.23.3.12 |url=http://thejns.org/doi/abs/10.3171/foc.2007.23.3.12?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov}}</ref> and metastatic [[breast cancer]]. It is also used by [[bodybuilding|bodybuilders]]. |
'''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]]<ref name="pmid17961023">{{cite journal |vauthors =Gross BA, Mindea SA, Pick AJ, Chandler JP, Batjer HH |title=Medical management of Cushing disease |journal=Neurosurgical focus |volume=23 |issue=3 |pages=E10 |year=2007 |pmid=17961023 |doi=10.3171/foc.2007.23.3.12 |url=http://thejns.org/doi/abs/10.3171/foc.2007.23.3.12?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov}}</ref> and metastatic [[breast cancer]]. It is also used by [[bodybuilding|bodybuilders]]. |
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== |
==Medical uses== |
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⚫ | |||
⚫ | |||
⚫ | |||
⚫ | # It blocks [[aromatase]]<ref name="pmid17602675">{{cite journal |vauthors =Siraki AG, Bonini MG, Jiang J, Ehrenshaft M, Mason RP |title=Aminoglutethimide-induced protein free radical formation on myeloperoxidase: a potential mechanism of agranulocytosis |journal=[[Chemical research in toxicology]] |volume=20 |issue=7 |pages=1038–45 |date=July 2007 |pmid=17602675 |pmc=2073000 |doi=10.1021/tx6003562}}</ref> in the generation of [[estrogens]] from [[androstenedione]] and [[testosterone]]. |
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⚫ | |||
==Non-medical uses== |
|||
⚫ | |||
⚫ | 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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⚫ | 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. |
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==Side effects== |
==Side effects== |
||
Its side effects are skin rash, [[hepatotoxicity]], inhibition of [[cortisol]] in the human body, and it may also cause [[hypothyroidism]]{{Citation needed|date=June 2008}}. Since cortisol helps break down [[muscle]], aminoglutethimide is used by [[bodybuilders]] in a [[steroid cycle]]. |
Its side effects are skin rash, [[hepatotoxicity]], inhibition of [[cortisol]] in the human body, and it may also cause [[hypothyroidism]]{{Citation needed|date=June 2008}}. Since cortisol helps break down [[muscle]], aminoglutethimide is used by [[bodybuilders]] in a [[steroid cycle]]. |
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== |
==Pharmacology== |
||
⚫ | |||
⚫ | |||
⚫ | # It blocks [[aromatase]]<ref name="pmid17602675">{{cite journal |vauthors =Siraki AG, Bonini MG, Jiang J, Ehrenshaft M, Mason RP |title=Aminoglutethimide-induced protein free radical formation on myeloperoxidase: a potential mechanism of agranulocytosis |journal=[[Chemical research in toxicology]] |volume=20 |issue=7 |pages=1038–45 |date=July 2007 |pmid=17602675 |pmc=2073000 |doi=10.1021/tx6003562}}</ref> in the generation of [[estrogens]] from [[androstenedione]] and [[testosterone]]. |
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⚫ | |||
⚫ | |||
⚫ | |||
==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|date=June 2011}} |
||
⚫ | 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. |
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==See also== |
==See also== |
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{{Androgens and antiandrogens}} |
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{{Antiandrogens}} |
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{{Estrogens and antiestrogens}} |
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{{Antiestrogens}} |
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{{Glucocorticoids and antiglucocorticoids}} |
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{{Antiglucocorticoids}} |
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{{Mineralocorticoids and antimineralocorticoids}} |
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{{Antimineralocorticoids}} |
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[[Category:11β-Hydroxylase inhibitors]] |
[[Category:11β-Hydroxylase inhibitors]] |
Revision as of 04:07, 25 November 2017
![]() | |
Clinical data | |
---|---|
Trade names | Cytadren, others |
AHFS/Drugs.com | Consumer Drug Information |
MedlinePlus | a604039 |
Pregnancy category |
|
Routes of administration | By mouth |
Drug class | Aromatase inhibitor; Antiestrogen; Steroidogenesis inhibitor; Antiglucocorticoid |
ATC code | |
Pharmacokinetic data | |
Bioavailability | >95% |
Metabolism | Liver |
Elimination half-life | 12.5 ± 1.6 hours |
Excretion | Urine |
Identifiers | |
| |
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) | |
| |
| |
(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.
Medical 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 second or third line choice for the treatment of hormone-sensitive (estrogen and progesterone) metastatic breast cancer.
Non-medical uses
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.
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.
Pharmacology
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.
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