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効能
副腎皮質抑制薬, 抗悪性腫瘍薬, エストロゲン生合成阻害薬
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説明
Aminoglutethimide is an aromatase inhibitor (IC50 = 7.5 μM). Aromatase inhibitors, including aminoglutethimide, inhibit estrogen synthesis via aromatase, suppressing estrogen levels in post-menopausal women. Formulations containing aromatase inhibitors have been used to treat estrogen receptor-positive breast cancer in post-menopausal women.
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化学的特性
White Solid
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使用
Aminoglutethimide is used to decrease the production of sex hormones and suppress the growth of tumors that need sex hormones to grow. 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 a drug of abuse by body builders.
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適応症
Aminoglutethimide (Cytadren) is a competitive inhibitor
of desmolase, the enzyme that catalyzes the conversion
of cholesterol to pregnenolone; it also inhibits
11-hydroxylase activity.This drug also reduces estrogen
production by inhibiting the aromatase enzyme complex
in peripheral (skin, muscle, fat) and steroid target
tissues.
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定義
ChEBI: A dicarboximide that is a six-membered cyclic compound having ethyl and 4-aminophenyl substituents at the 3-position.
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世界保健機関（WHO）
Aminoglutethimide, a weak anticonvulsant, was introduced in
1960 for use in the treatment of epilepsy. However, its adrenocortical suppressant
activity gave rise to serious adverse effects. The FDA decision in 1966 was taken in
respect of a preparation indicated in epilepsy. In 1980 preparations containing
aminoglutethimide were reintroduced in the USA exclusively for the treatment of
Cushing's disease. In 1986 they were also registered in Saudi Arabia for use in
Cushing's syndrome and for the treatment of breast cancer. In some other
countries these preparations are additionally approved for carcinoma of the
prostate.
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一般的な説明
Aminoglutethimide, 3-(4-aminophenyl)-3-ethyl-2,6-piperidinedione, is mainly usedto treat Cushing syndrome, a condition of adrenal steroidexcess, a use in which the P450scc inhibition of thiscompound is exploited rather than its aromatase inhibition.Aminoglutethimide is a weak inhibitor of aromataseand has been used successfully in the treatment of estrogen-dependent breast cancer. Because of the developmentof more selective aromatase inhibitors, the use ofaminoglutethimide for its ability to inhibit aromatase is notsupported.
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作用機序
This drug blocks the transformation of cholesterol into pregnenolone, and androgens into
estrogens in the adrenal glands, thus completely suppressing the production of all steroid
hormones. Aminoglutethimide is used for palliative treatment of prostate carcinomas and
post-menopausal breast carcinomas. Synonyms of aminoglutethimide are orimeten, citadren and others.
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臨床応用
Aminoglutethimide is suitable for use in Cushing’s
syndrome that results from adrenal carcinoma and in
congenital adrenal hyperplasia, in which it protects the
patient from excessive secretion of endogenous androgens.
The drug is not curative, and relapse occurs when
treatment is terminated. Since aminoglutethimide therapy
is frequently associated with mineralocorticoid deficiency,
mineralocorticoid supplements may be needed.
Aminoglutethimide and metyrapone are frequently
used in combination at lower doses of both drugs as an
adjunct to radiation or surgical therapy.
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副作用
Such a medical adrenalectomy is an efficacious
treatment for metastatic breast and prostate cancer,
since it diminishes the levels of circulating sex hormones.
Glucocorticoids are administered concomitantly
to suppress enhanced corticotrophin release. Cortisol is
preferable to dexamethasone in this situation because
aminoglutethimide markedly enhances the hepatic
microsomal metabolism of dexamethasone. Hepatic enzyme
induction may be responsible for the development
of tolerance to the side effects of aminoglutethimide,
such as ataxia, lethargy, dizziness, and rashes.
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代謝経路
Following administration of a single oral dose of 14C-
aminoglutethimide to rats, guinea pigs, rabbits, and
man, more than 89% of the dose is excreted in urine
and feces within 72h, and dogs eliminate only 51% in
this time. Extensive metabolism occurs in all species,
with N-acetylaminoglutethimide being the major
metabolite except for dogs and man. In the latter two
species, the unchanged drug is the main product
excreted. As shown in the pathways, it appears that
aminoglutethimide is metabolized by several pathways
in man and, of the ten metabolites, only two are present
in any quantity, namely N-acetylaminoglutethimide and
N-hydroxyaminoglutethimide, the latter increasing during
the course of treatment.
