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外観
白色～ほとんど白色粉末～結晶
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用途
医薬(副腎皮質ホルモン合成阻害剤)
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効能
抗悪性腫瘍薬, ステロイド合成阻害薬
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商品名
オペプリム (ヤクルト本社)
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説明
Mitotane is an inhibitor of steroidogenesis that suppresses the growth of adrenocortical cells. It blocks the expression of several genes that encode proteins involved in steroidogenesis and disrupts mitochondrial respiratory chain activity in human adrenocortical cells. Mitotane has anti-neoplastic actions, alone or in combination with other compounds, and suppresses cortisol synthesis, although it also has significant toxicity in the gastrointestinal tract and nervous system. It is effective against adrenocortical carcinoma and Cushing’s Syndrome in clinical trials.
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化学的特性
Crystalline Solid
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使用
Mitotane is an inhibitor of steroidogenesis that suppresses the growth of adrenocortical cells. It blocks the expression of several genes that encode proteins involved in steroidogenesis and disrupts mitochondrial respiratory chain activity in human adrenocortical cells. Mitotane has anti-neoplastic actions, alone or in combination with other compounds, and suppresses cortisol synthesis, although it also has significant toxicity in the gastrointestinal tract and nervous system. It is effective against adrenocortical carcinoma and Cushing’s Syndrome in clinical trials.
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適応症
Mitotane (Lysodren) produces selective atrophy of the
zona fasciculata and zona reticularis, which results in a
decrease in the secretion of 17-hydroxycorticosteroids.
Direct inhibition of cholesterol side-chain cleavage and
11/18-hydroxylase activities has also been demonstrated.
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一般的な説明
Colorless powder.
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空気と水の反応
Insoluble in water.
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反応プロフィール
Mitotan dehydrohalogenates with strong alkalis. Simple aromatic halogenated organic compounds are very unreactive; halogenated aliphatic compounds are moderately or very reactive. For both subgroups, reactivity generally decreases with increased degree of substitution of halogen for hydrogen atoms. Materials in this group are incompatible with strong oxidizing and reducing agents. Also, they are incompatible with many amines, nitrides, azo/diazo compounds, alkali metals, and epoxides.
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火災危険
Flash point data for Mitotan are not available. Mitotan is probably combustible.
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薬理学
Mitotane, a derivative of the insecticide DDT, quickly lowers the level of corticosteroids,
and is metabolized in the blood and urine and used on non-operable metastatic prostate
carcinomas. Synonyms of this drug are lysodren and others.
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臨床応用
Mitotane is the drug of choice for the treatment of
primary adrenal carcinoma when surgery or radiation
therapy is not feasible. Its effectiveness
in curtailing adrenal activity is due to an action on
adrenocortical mitochondria to impair cytochrome
P450 steps in steroid biosynthesis. Mitotane requires
metabolic transformation to exert its therapeutic action,
and the differential ability of tumors to metabolize
the drug may determine its clinical effectiveness. It is
advised to measure serum mitotane levels and urinary
free cortisol excretion to ensure adequate therapeutic
concentrations. Mitotane increases circulating cholesterol
by inhibiting cytochrome P450–mediated reactions
and therefore contributes to the cardiovascular
events that are a significant cause of mortality in untreated
Cushing’s syndrome.
Mitotane, being closely related to the organochlorine
insecticides, shares its inductive effects on the liver
microsomal drug-metabolizing enzyme system, and its
use may therefore alter the requirement for concomitantly
administered drugs that are also metabolized by
this pathway.
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副作用
Mitotane is capable of inducing remission of
Cushing’s disease, but only after several weeks of therapy
and at the price of severe gastrointestinal distress.
Moreover, more than half of patients relapse following
cessation of therapy. Other side effects include lethargy,
mental confusion, skin rashes, and altered hepatic function.
Being a lipid-soluble substance, mitotane remains
stored in body tissues for extended periods. This may
account for the marked patient-to-patient variability in
its therapeutic and/or toxic effects.
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純化方法
Purify Mitotane by recrystallisation from pentane, MeOH or EtOH. It is soluble in isooctane and CCl4. [Haller et al. J Am Chem Soc 67 1600 1945, Beilstein 5 IV 1883.]
