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Revision as of 15:09, 21 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank').← Previous edit		Latest revision as of 15:19, 8 October 2024 edit undoJWBE (talk | contribs)Extended confirmed users10,126 edits added Category:4-Aminophenyl compounds using HotCat
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			{{Short description|Group of stereoisomers}}
			{{Use dmy dates|date=December 2022}}
	{{Drugbox		{{Drugbox
			| Verifiedfields = verified
	| verifiedrevid = 443384146
			| Watchedfields = verified
	| IUPAC_name = 3-(4-aminophenyl)-3-ethyl-piperidine-2,6-dione
			| verifiedrevid = 456688404
			| IUPAC_name = (''RS'')-3-(4-aminophenyl)-3-ethyl-piperidine-2,6-dione
	| image = Aminoglutethimide.svg		| image = Aminoglutethimide.svg
	| width = 220		| width = 185px
			| image2 = Aminoglutethimide molecule ball.png
			| width2 = 185px
	<!--Clinical data-->		<!--Clinical data-->
	| tradename =		| tradename = Elipten, Cytadren, Orimeten, numerous others
	| Drugs.com = {{drugs.com|CDI|aminoglutethimide}}		| Drugs.com = {{drugs.com|CDI|aminoglutethimide}}
	| MedlinePlus = a604039		| MedlinePlus = a604039
	| pregnancy_AU = D		| pregnancy_AU = D
	| pregnancy_US = D		| pregnancy_US = D
	| routes_of_administration = ]		| routes_of_administration = ]
			| class = ]; ]; ]; ]
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| bioavailability = >95%		| bioavailability = Rapid, complete<ref name="TindallSedrak2013" />
			| protein_bound =
	| metabolism = ]
			| metabolism = ] (minimal; ])<ref name="TindallSedrak2013" />
	| elimination_half-life = 12.5 ± 1.6 hours
			| metabolites =
	| excretion = ]
			| elimination_half-life = 12.5 hours<ref name="TindallSedrak2013" />
			| excretion = ] (34–54%, unchanged)<ref name="TindallSedrak2013" />
	<!--Identifiers-->		<!--Identifiers-->
	| CASNo_Ref = {{cascite|correct|CAS}}		| CAS_number_Ref = {{cascite|correct|CAS}}
	| CAS_number = 125-84-8		| CAS_number = 125-84-8
			| CAS_supplemental = <br />31075-85-1 (])
	| ATC_prefix = L02		| ATC_prefix = L02
	| ATC_suffix = BG01		| ATC_suffix = BG01
	| PubChem = 2145		| PubChem = 2145
			| IUPHAR_ligand = 7054
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank = DB00357		| DrugBank = DB00357
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	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 488		| ChEMBL = 488
			| synonyms = AG; AGI; Ba 16038; Ciba 16038; ND-1966; 2-(''p''-Aminophenyl)-2-ethylglutarimide
	<!--Chemical data-->		<!--Chemical data-->
	| C=13 | H=16 | N=2 | O=2		| C=13 | H=16 | N=2 | O=2
			| chirality = ]
	| molecular_weight = 232.278 ]/]
	| smiles = O=C1NC(=O)CCC1(c2ccc(N)cc2)CC		| SMILES = O=C1NC(=O)CCC1(c2ccc(N)cc2)CC
	| InChI = 1/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)
	| InChIKey = ROBVIMPUHSLWNV-UHFFFAOYAT
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| 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''' ('''AG'''), sold under the brand names '''Elipten''', '''Cytadren''', and '''Orimeten''' among others, is a medication which has been used in the treatment of ]s, ], ], and ], among other indications.<ref name="Milne2018">{{cite book| vauthors = Milne GW |title=Drugs: Synonyms and Properties: Synonyms and Properties|url=https://books.google.com/books?id=xUlaDwAAQBAJ&pg=PT1182|year=2018|publisher=Taylor & Francis|isbn=978-1-351-78989-9|pages=1182–}}</ref><ref name="MortonHall2012">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA14|year=2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=14–}}</ref><ref name="FiggChau2010">{{cite book| vauthors = Friedlander TW, Ryan CJ | chapter = Adrenal Androgen Synthesis Inhibitor Therapies in Castrate-Resistant Prostate Cancer | veditors = Figg WD, Chau CH, Small EJ |title=Drug Management of Prostate Cancer| chapter-url=https://books.google.com/books?id=4KDrjeWA5-UC&pg=PA93|year=2010|publisher=Springer Science & Business Media|isbn=978-1-60327-829-4|pages=91–96}}</ref><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=1–6 |year=2007 |pmid=17961023 |doi=10.3171/foc.2007.23.3.12 |doi-access=free }}</ref><ref name="Osborne2012" /><ref name="Llewellyn2011" /> It has also been used by ]s, ]s, and other men for ] and ]s.<ref name="Llewellyn2011">{{cite book|author=William Llewellyn|title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC&pg=PT770|year=2011|publisher=Molecular Nutrition Llc|isbn=978-0-9828280-1-4|pages=770–}}</ref><ref name="TindallSedrak2013" /> AG is taken ] three or four times per day.<ref name="WilkesBarton-Burke2013" /><ref name="FiggChau2010" />
	'''Aminoglutethimide''' is an anti-] drug marketed under the tradename '''Cytadren''' by ] around the world. It blocks the production of steroids derived from ] and is clinically used in the treatment of ]<ref name="pmid17961023">{{cite journal |author=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 ]. It is also used by ].
			]s of AG include ], ], ], ], ], ], ], ], and ], among others.<ref name="FiggChau2010" /> AG is both an ] and a ].<ref name="MortonHall2012" /><ref name="FiggChau2010" /> In terms of the latter property, it ]s ]s such as ] (CYP11A1, P450scc) and ] (CYP19A1), thereby inhibiting the conversion of ] into ]s and blocking the ] of ]s, ]s, and ]s, among other ] ]s.<ref name="FiggChau2010" /> As such, AG is an ] and ], including both an ] and a ].<ref name="Patrick2013" /><ref name="SmithWilliams2005" /><ref name="Ebadi2007" /><ref name="Osborne2012" /><ref name="Llewellyn2011" />
	==Mechanism==
	Aminoglutethimide has two mechanisms of action:
			AG was introduced for medical use, as an anticonvulsant, in 1960.<ref name="Sneader2005" /><ref name="HarrapDavis2012" /> It was withdrawn in 1966 due to ].<ref name="Sneader2005" /><ref name="HarrapDavis2012" /> Its steroidogenesis-inhibiting properties were discovered serendipitously and it was subsequently repurposed for use in the treatment of Cushing's syndrome, breast cancer, and prostate cancer from 1969 and thereafter.<ref name="Patrick2013" /><ref name="HarrapDavis2012" /><ref name="Osborne2012" /> However, although used in the past, it has mostly been superseded by newer agents with better ] and lower toxicity such as ], ], and other aromatase inhibitors.<ref name="FiggChau2010" /><ref name="Patrick2013" /> It remains marketed only in a few countries.<ref name="Drugs.com">{{Cite web|url=https://www.drugs.com/drug-class/aromatase-inhibitors.html|title=List of Aromatase inhibitors|website=Drugs.com}}</ref><ref name="Llewellyn2011" />
	# It blocks ]<ref name="pmid17602675">{{cite journal |author=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 |year=2007 |month=July |pmid=17602675 |pmc=2073000 |doi=10.1021/tx6003562}}</ref> in the generation of ] from ] and ].
	# It blocks the conversion of cholesterol to ] by inhibiting the enzyme ] and consequently decreases synthesis of all hormonally active ].
			==Medical uses==
	At low doses, aminogluthethimide is only an effective inhibitor of aromatase, but at higher doses, it effectively blocks P450scc as well.
			AG is used as an anticonvulsant in the treatment of ] and as a steroidogenesis inhibitor in the treatment of Cushing's syndrome, ] breast cancer, and prostate cancer.<ref name="Castro2013">{{cite book| vauthors = Hendy WF | chapter = Adrenalectomy and hypophysectomy in disseminated prostate cancer | veditors = Castro JE |title=The Treatment of Prostatic Hypertrophy and Neoplasia| chapter-url=https://books.google.com/books?id=Nc8hBQAAQBAJ&pg=PA179|year=2013|publisher=Springer Science & Business Media|isbn=978-94-015-7190-6|pages=179–}}</ref><ref name="Osborne2012" /><ref name="Sneader2005" /><ref name="Llewellyn2011" /> It is also used to treat ], ], ], and ] ] (ACTH) producing ]s.<ref name="MortonHall2012" /><ref name="TindallSedrak2013" /><ref name="Krieger2012">{{cite book| vauthors = Krieger DT | chapter = Chapter 8: Treatment of Cushing's Disease and Syndrome: Adrenocortical Carcinoma: Aminoglutethimide |title=Cushing's Syndrome| chapter-url = https://books.google.com/books?id=b663BgAAQBAJ&pg=PT200|year=1982|publisher=Springer Science & Business Media|isbn=978-3-642-81659-8|pages=120}}</ref> When used as a steroidogenesis inhibitor to treat breast cancer and prostate cancer, AG is given in combination with ], ], or an equivalent ] to prevent ].<ref name="FiggChau2010" /><ref name="Osborne2012" /> AG is a second- or third-line choice in the treatment of ] ] breast cancer. While effective in the treatment of breast cancer in postmenopausal women, it is not effective in ] women and is not an effective ] steroidogenesis inhibitor, probably because it is not a ] enough ].<ref name="Osborne2012" /><ref name="Priestman2012" /> The medication is effective in the treatment of prostate cancer, but its effectiveness is low and inconsistent, likely due to its relatively weak steroidogenesis inhibition and poor ].<ref name="Osborne2012" /> Nonetheless, AG was found to be non-significantly different in effectiveness from ] in terms of prostate cancer ] regression.<ref name="Osborne2012" /> In any case, AG is not recommended as a first-line therapy in prostate cancer, but instead only as a second-line therapy.<ref name="Osborne2012" /><ref name="Priestman2012" /> It has only rarely been used in the treatment of prostate cancer.<ref name="FiggChau2010" />
			AG is used for adrenal steroidogenesis inhibition ] at a dosage of 250&nbsp;mg three times per day (750&nbsp;mg/day total) for the first 3&nbsp;weeks of therapy and then increased to 250&nbsp;mg four times per day (1,000&nbsp;mg/day total) thereafter.<ref name="FiggChau2010" /> It can be used at a dosage of up to 500&nbsp;mg four times per day (2,000&nbsp;mg/day).<ref name="TindallSedrak2013" /><ref name="WilkesBarton-Burke2013" /> It is used as an ] to inhibit ] estrogen production by mouth at a dosage of 125&nbsp;mg twice per day (250&nbsp;mg/day total), without significant suppression of adrenal steroidogenesis at this dosage.<ref name="Priestman2012" /> Maximal aromatase inhibition is said to occur between dosages of 250 to 500&nbsp;mg per day.<ref name="Llewellyn2011" /> The side effects of AG are less frequent and severe at this dosage.<ref name="Priestman2012" /> However, they are still less when AG is combined with hydrocortisone, and so AG is generally combined with a corticosteroid even at this lower dosage.<ref name="Priestman2012" /> AG should only be used under close ] and with ]s including ], ], ], ], and ].<ref name="TindallSedrak2013" /><ref name="WilkesBarton-Burke2013" />
			] can achieve similar decreases in steroid hormone levels as AG but is more effective in promoting ] regression and is moderately less toxic in comparison.<ref name="FiggChau2010" /> AG can still be a useful alternative in those who have failed or are unable to ] ketoconazole and other therapies however.<ref name="FiggChau2010" />
			===Available forms===
			AG is provided most commonly in the form of 250&nbsp;mg ]s.<ref name="Llewellyn2011" /><ref name="WilkesBarton-Burke2013" />
			==Non-medical uses==
			AG is used by ]s, ]s, and other men to lower circulating levels of ] in the body and thereby prevent ].<ref name="Llewellyn2011" /><ref name="TindallSedrak2013" /> Cortisol is ] to ] in ] and effective suppression of cortisol by AG at high doses can prevent muscle loss.<ref name="Llewellyn2011" /> It is usually used in combination with an ] to avoid ].<ref name="Llewellyn2011" /> However, the usefulness of AG for such purposes has been questioned, with few users reportedly having positive comments about it, and the risks of AG are said to be high.<ref name="Llewellyn2011" /><ref name="TindallSedrak2013" /> In any case, AG is also used by bodybuilders and other men for its actions as an aromatase inhibitor in order to decrease estrogen levels.<ref name="Llewellyn2011" /> It is said to be useful for inhibiting the estrogenic side effects of certain anabolic steroids such as ], increased ], and ].<ref name="Llewellyn2011" />
			==Contraindications==
			AG should not be used in people with known ] to AG.<ref name="TindallSedrak2013" /> It should not be used in women who are ] or ].<ref name="TindallSedrak2013" /> Other potential contraindications include ], ] (herpes zoster), ], ], ], and ].<ref name="TindallSedrak2013" />
	==Side effects==		==Side effects==
			AG has many ]s and is a relatively ] medication, although its side effects are described as usually relatively mild.<ref name="FiggChau2010" /><ref name="Osborne2012" /> The side effects of AG include ], ], ], ], ], ], ], ], ]s, ], ], ], ], ], ], ], ] or ], ], ], ], ], ], ], ], ], ]s, ], ]s, and ] (e.g., ], ], others).<ref name="FiggChau2010" /><ref name="Osborne2012" /><ref name="Priestman2012" /><ref name="Llewellyn2011" /><ref name="TindallSedrak2013" /><ref name="WilkesBarton-Burke2013" /> Lethargy is the most common side effect and has been found to occur in 31 to 70% of people treated with AG.<ref name="Osborne2012" /> It is the most common reason for discontinuation of AG.<ref name="Osborne2012" /> Skin rash and hypotension have both been observed in about 15% of people.<ref name="Osborne2012" /> At least one side effect will occur in 45 to 85% of people.<ref name="Osborne2012" /> Severe toxicity is seen in 10% of people, including ] thought to be due to adrenal insufficiency.<ref name="Osborne2012" /> ] and ], including marked depression of ], ]s, or both, occurs rarely, with an incidence of about 0.9%.<ref name="Osborne2012" /><ref name="PonderWaring2012">{{cite book| vauthors = Waxman J, Jane N | chapter = New endocrine therapies for cancer | veditors = Ponder BA, Waring MJ |title=The Science of Cancer Treatment| chapter-url = https://books.google.com/books?id=EbGvBQAAQBAJ&pg=PA48|year=2012|publisher=Springer Science & Business Media|isbn=978-94-009-0709-6|pages=48–}}</ref> It is usually seen within the first 7&nbsp;weeks of treatment and resolves within 3&nbsp;weeks following discontinuation.<ref name="Osborne2012" /> AG is discontinued in 5 to 10% of people due to intolerable side effects.<ref name="Osborne2012" /> The ] side effects of AG are due to its nature as an anticonvulsant and relation to ].<ref name="Priestman2012" />
	Its side effects are skin rash, ], inhibition of ] in the human body, and it may also cause ]{{Citation needed|date=June 2008}}. Since cortisol helps break down ], aminoglutethimide is used by ] in a ].
	==Clinical uses==		==Overdose==
			In the event of ] of AG, ], ], ], ], and ] may occur.<ref name="Upfal2006">{{cite book| vauthors = Upfal J |title=The Australian Drug Guide: Every Person's Guide to Prescription and Over-the-counter Medicines, Street Drugs, Vaccines, Vitamins and Minerals...|url=https://books.google.com/books?id=7O9kiqN2q2YC&pg=PA45|year=2006|publisher=Black Inc.|isbn=978-1-86395-174-6|pages=45–}}</ref><ref name="Springhouse2000">{{cite book|title=Nurse Practitioner's Drug Handbook|url=https://books.google.com/books?id=I6Jt1THMB_4C|year=2000|publisher=Springhouse Corp.|pages=40–41|isbn = 9780874349979}}</ref> Medical attention should be sought urgently.<ref name="Upfal2006" /> Treatment of AG overdose can include ] to decrease ] and ] to enhance ].<ref name="Convention2006">{{cite book|author=United States Pharmacopeial Convention|title=USP DI: United States Pharmacopeia Dispensing Information|url=https://books.google.com/books?id=hMpKAQAAIAAJ|year=2006|publisher=United States Pharmacopeial Convention|isbn=978-1-56363-429-1|pages=75–76}}</ref>
	Aminoglutethimide is indicated in conjunction with other drugs for the suppression of ] function in patients with ].
			==Interactions==
	It is also a 2nd or 3rd line choice for the treatment of ] sensitive (] and ]) ] ].
			AG has an ] with all corticosteroids.<ref name="TindallSedrak2013" /> It enhances the metabolism of ], so hydrocortisone should be used instead.<ref name="WilkesBarton-Burke2013" /> If the person is taking ], the dosage of warfarin may need to be increased.<ref name="WilkesBarton-Burke2013" /> ] potentiates the ] side effects of AG.<ref name="WilkesBarton-Burke2013" /> Dosages of ], ], and ] may need to be increased.<ref name="WilkesBarton-Burke2013" />
	==Abuse==		==Pharmacology==
	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 ] to protein in muscle and effective blockade of P450scc by aminogluthethimide at high doses prevents muscle loss.{{Citation needed|date=June 2011}}
			===Pharmacodynamics===
	==References==
			AG is a ] and ] ], acting as a ] and ] of multiple ]s, including:<ref name="Patrick2013" /><ref name="SmithWilliams2005">{{cite book| vauthors = Patel A, Smith HJ, Steinmetzer T | chapter = Design of Enzyme Inhibitors and Drugs | veditors = Smith HJ, Williams W |title=Smith and Williams' Introduction to the Principles of Drug Design and Action | edition = Fourth | chapter-url = https://books.google.com/books?id=P2W6B9FQRKsC&pg=PA281|year=2005|publisher=CRC Press|isbn=978-0-203-30415-0|pages=281–}}</ref><ref name="Ebadi2007">{{cite book| vauthors = Ebadi M | chapter = Aminoglutethimide |title=Desk Reference of Clinical Pharmacology, Second Edition| chapter-url=https://books.google.com/books?id=ihxyHbnj3qYC&pg=PA63|year=2007|publisher=CRC Press|isbn=978-1-4200-4744-8|pages=63–}}</ref><ref name="Osborne2012">{{cite book| vauthors = Havlin KA, Trump DL | title = Aminoglutethimide: theoretical considerations and clinical results in advanced prostate cancer | veditors = Osborne CK | chapter = Endocrine Therapies in Breast and Prostate Cancer|chapter-url=https://books.google.com/books?id=gW0eBAAAQBAJ&pg=PA87|year=2012|publisher=Springer Science & Business Media|isbn=978-1-4613-1731-9|pages=39, 73, 87–93}}</ref><ref name="Llewellyn2011" />
	{{reflist}}
			* ] (CYP19A1) (600&nbsp;nM).<ref name="FiggChau2010" /><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=] |volume=20 |issue=7 |pages=1038–45 |date=July 2007 |pmid=17602675 |pmc=2073000 |doi=10.1021/tx6003562}}</ref> Inhibits the formation of the ]s ] and ] from ] and ], respectively.
	==External links==
			* ] (P450scc; CYP11A1) (~20,000&nbsp;nM).<ref name="FiggChau2010" /><ref name="Osborne2012" /> Inhibits the conversion of ] into ] and consequently decreases the synthesis of all ]s including the ]s, ]s, ]s, and ]s, as well as ]s.
	* (from the FDA website)
			* ] (CYP21A2).<ref name="Llewellyn2011" /> Prevents the conversion of ] and ] into ] and ], respectively.
	*
			* ] (CYP11B1).<ref name="Osborne2012" /><ref name="Llewellyn2011" /><ref name="HaschekBolon2017">{{cite book| vauthors = Wallig MA | chapter = Endocrine System | veditors = Haschek WM, Bolon B, Rousseaux CG, Wallig MA |title=Fundamentals of Toxicologic Pathology| chapter-url = https://books.google.com/books?id=M4yZDgAAQBAJ&pg=PA580|year=2017|publisher=Elsevier Science|isbn=978-0-12-809842-4|pages=580–}}</ref> Prevents the conversion of ] and ] into ] and ], respectively.
			* ] (18-hydroxylase; CYP11B2).<ref name="Osborne2012" /><ref name="Llewellyn2011" /> Prevents the conversion of corticosterone into ].<ref name="ThomasKeenan2012">{{cite book| vauthors = Thomas JA, Keenan EJ | chapter = Effects of Drugs on the Endocrine System |title=Principles of Endocrine Pharmacology| chapter-url=https://books.google.com/books?id=mTagBQAAQBAJ&pg=PA278|year=2012|publisher=Springer Science & Business Media|isbn=978-1-4684-5036-1|pages=278–}}</ref>
			As such, AG is an ] and ], including both an ] and a ].<ref name="Patrick2013" /><ref name="SmithWilliams2005" /><ref name="Ebadi2007" /><ref name="Osborne2012" /><ref name="Llewellyn2011" /> For these reasons, AG has functional ]ic, ]ic, ], and ] actions.<ref name="Patrick2013" /><ref name="SmithWilliams2005" /><ref name="Ebadi2007" /><ref name="Osborne2012" /><ref name="Llewellyn2011" /> In terms of its actions as an adrenal steroidogenesis inhibitor, it is described as a form of reversible "medical adrenalectomy" or "chemical adrenalectomy".<ref name="FiggChau2010" /><ref name="Osborne2012" /><ref name="WilkesBarton-Burke2013">{{cite book| vauthors = Wilkes GM, Barton-Burke M | chapter = Introduction to Chemotherapy Drugs |title=2014 Oncology Nursing Drug Handbook| chapter-url=https://books.google.com/books?id=sM2FAgAAQBAJ&pg=PA50|year=2013|publisher=Jones & Bartlett Publishers|isbn=978-1-284-05374-6|pages=50–52}}</ref> While AG inhibits all of the enzymes listed above, inhibition of P450scc is primarily responsible for its inhibition of ] ].<ref name="JonesMohr2012">{{cite book | vauthors = Zak F | chapter = Lipid Hyperplasia, Adrenal Cortex, Rat | series = Monographs on Pathology of Laboratory Animals | veditors = Jones TC, Mohr U, Hunt RD |title=Endocrine System| chapter-url = https://books.google.com/books?id=UTfvCAAAQBAJ&pg=PA83|year=2012|publisher=Springer Science & Business Media|isbn=978-3-642-96720-7|pages=83– | doi = 10.1007/978-3-642-60996-1_65 }}</ref> In terms of ]s, AG has been shown to significantly suppress ], ], testosterone, and ] levels in men.<ref name="Osborne2012" /> Although it is most potent in inhibiting aromatase among the enzymes it targets, AG is described nonetheless as a relatively weak ].<ref name="Ebadi2007" /><ref name="FiggChau2010" /> In addition, it is described as a much more potent aromatase inhibitor than adrenal steroidogenesis inhibitor.<ref name="Priestman2012">{{cite book| vauthors = Priestman TJ |title=Cancer Chemotherapy: an Introduction|url=https://books.google.com/books?id=wGlyBgAAQBAJ&pg=PT178|year=2012|publisher=Springer Science & Business Media|isbn=978-1-4471-1686-8|pages=178–}}</ref> AG can inhibit aromatase by 74 to 92% and decrease circulating estradiol levels by 58 to 76% in men and postmenopausal women.<ref name="TindallSedrak2013" /><ref name="Llewellyn2011" /> AG is not an effective ] steroidogenesis inhibitor in premenopausal women.<ref name="Priestman2012" /> However, interference with ovarian steroidogenesis by AG may in any case result in ] and ] in premenopausal women.<ref name="WilkesBarton-Burke2013" /><ref name="Llewellyn2011" />
	==See also==
	* ]
			{{Pharmacodynamics of aromatase inhibitors}}
	{{Sex hormones}}
	{{Corticosteroids}}
			===Pharmacokinetics===
			With ], the ] of AG is rapid and complete.<ref name="TindallSedrak2013">{{cite book| vauthors = House AA, Tindall WN, Sedrak MM | chapter = Drugs Used to Treat Endocrine Gland Disorders | veditors = Tindall WN, Sedrak M, Boltri J |title=Patient-Centered Pharmacology: Learning System for the Conscientious Prescribe| chapter-url = https://books.google.com/books?id=-Q_TAQAAQBAJ&pg=PA218|year=2013|publisher=F.A. Davis|isbn=978-0-8036-4070-2|pages=218–}}</ref> It is ] throughout the body.<ref name="TindallSedrak2013" /> In terms of ], a portion of AG is ] in the ].<ref name="TindallSedrak2013" /> The ] of AG is 12.5&nbsp;hours.<ref name="TindallSedrak2013" /> It is ] in ] 34 to 54% unchanged.<ref name="TindallSedrak2013" />
			==Chemistry==
			AG is a ] ], specifically a ], and is a ] of ].<ref name="MortonHall2012" /><ref name="Sneader2005" /><ref name="Llewellyn2011" /> It is also known by its chemical names 2-(4-aminophenyl)-2-ethylglutarimide and 2-(aminophenyl)-3-ethylpiperidine-2,6-dione.<ref name="Elks2014" /><ref name="Llewellyn2011" /> Aside from glutethimide, AG is structurally related to ] (pyridoglutethimide) and ], as well as ], ], and ].<ref name="SmithWilliams2005"/><ref name="Wiley-VCH2005">{{cite book |title=Ullmann's Industrial Toxicology|url=https://books.google.com/books?id=r-4JAQAAMAAJ|year=2005|publisher=Wiley|isbn=978-3-527-31247-4|page=876}}</ref><ref name="Bentley1980">{{cite book| vauthors = Bentley PJ | chapter = Steroid Hormones |title=Endocrine Pharmacology: Physiological Basis and Therapeutic Applications| chapter-url = https://books.google.com/books?id=W6M9AAAAIAAJ&pg=PA143|year=1980|publisher=CUP Archive|isbn=978-0-521-22673-8|pages=143, 162–163}}</ref><ref name="Selye2013">{{cite book | vauthors = Selye H | chapter = Stressors and Conditioning Agents |title=Stress in Health and Disease| chapter-url = https://books.google.com/books?id=wrfYBAAAQBAJ&pg=PA57 |year=2013|publisher=Elsevier Science|isbn=978-1-4831-9221-5|pages=57–}}</ref><ref name="Sneader2005" />
			==History==
			AG was introduced for medical use, as an ], in 1960.<ref name="Sneader2005">{{cite book| vauthors = Sneader W | chapter = The First Synthetic Drugs and Their Analogues |title=Drug Discovery: A History| chapter-url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA367|year=2005|publisher=John Wiley & Sons|isbn=978-0-471-89979-2 | doi = 10.1002/0470015535.ch26 |pages=367–}}</ref><ref name="HarrapDavis2012">{{cite book| vauthors = Jackson IM | chapter = Aminoglutethimide (Orimeten): The Present and the Future | veditors = Harrap LR, Davis W, Calvert AH |title=Cancer Chemotherapy and Selective Drug Development: Proceedings of the 10th Anniversary Meeting of the Coordinating Committee for Human Tumour Investigations, Brighton, England, October 24–28, 1983| chapter-url=https://books.google.com/books?id=y3bjBwAAQBAJ&pg=PA481|year=2012|publisher=Springer Science & Business Media|isbn=978-1-4613-3837-6|pages=481– | doi = 10.1007/978-1-4613-3837-6_73 }}</ref> In 1963, it was reported that AG had induced symptoms of ] (]) in a young girl.<ref name="Sneader2005" /> Following additional reports, it was determined that AG acts as a steroidogenesis inhibitor.<ref name="Sneader2005" /> As such, the discovery of AG as a steroidogenesis inhibitor was serendipitous.<ref name="Patrick2013">{{cite book| vauthors = Patrick G | chapter = Drug Discovery: Finding a Lead |title=An Introduction to Medicinal Chemistry| chapter-url = https://books.google.com/books?id=Pj7xJRuhZxUC&pg=PA208|year=2013|publisher=OUP Oxford|isbn=978-0-19-969739-7|pages=208–,539}}</ref> The medication was withdrawn from the market in 1966 due to its adverse effects.<ref name="Sneader2005" /><ref name="HarrapDavis2012" /> The first report of AG in the treatment of ] was published in 1969, and the first report of AG in the treatment of ] was published in 1974.<ref name="HarrapDavis2012" /><ref name="Osborne2012" /> The medication was one of the first adrenal steroidogenesis inhibitors as well as the first aromatase inhibitor to be discovered and used clinically, and led to the development of other aromatase inhibitors.<ref name="PonderWaring2012" /><ref name="FiggChau2010" /><ref name="Furr2008">{{cite book| vauthors = Miller WR | chapter = Background and development of aromatase inhibitors | veditors = Furr BJ |title=Aromatase Inhibitors| chapter-url = https://books.google.com/books?id=dyg9Ab3FsVgC&pg=PA4|year=2008|publisher=Springer Science & Business Media|isbn=978-3-7643-8693-1|pages=4,101,127}}</ref><ref name="Patrick2013" /> Along with ], it is described as a "first-generation" aromatase inhibitor.<ref name="Llewellyn2011" /> AG has largely been superseded by medications with better effectiveness and ] and reduced toxicity, such as ], ], and other aromatase inhibitors.<ref name="FiggChau2010" /><ref name="Osborne2012" /><ref name="Patrick2013" />
			==Society and culture==
			===Generic names===
			''Aminoglutethimide'' is the ] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, and {{abbrlink|BAN|British Approved Name}}, while ''aminoglutéthimide'' is its {{abbrlink|DCF|Dénomination Commune Française}} and ''aminoglutetimide'' is its {{abbrlink|DCIT|Denominazione Comune Italiana}}.<ref name="Drugs.com" /><ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA70|year=2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=70–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA43|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=43–}}</ref><ref name="MortonHall2012" /> It is also known by its developmental code names ''Ba 16038'', ''Ciba 16038'', and ''ND-1966''.<ref name="Drugs.com" /><ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="MortonHall2012" />
			===Brand names===
			AG has been marketed under brand names including Elipten, Cytandren, and Orimeten.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Llewellyn2011" /><ref name="Drugs.com" /><ref name="MortonHall2012" /> It has also been marketed under other brand names such as Aminoblastin, Rodazol, and Mamomit, among numerous others.<ref name="IndexNominum2000" /><ref name="Llewellyn2011" />
			===Availability===
			AG appears to remain marketed only in a few countries, which include ], ], and ].<ref name="Drugs.com" /> Previously, AG was available very widely throughout the world, including in more than two dozen countries and under numerous brand names.<ref name="Llewellyn2011" /> Among other places, it was marketed in the ], ], the ], other ]an countries, ], ], ], ], ], ], and ].<ref name="IndexNominum2000" /><ref name="Llewellyn2011" />
			==References==
			{{Reflist}}
			{{Anticonvulsants}}
			{{Androgens and antiandrogens}}
			{{Estrogens and antiestrogens}}
			{{Glucocorticoids and antiglucocorticoids}}
			{{Mineralocorticoids and antimineralocorticoids}}
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	]