Aminoglutethimide (phosphate)

Aminoglutethimide phosphate (DL-Aminoglutethimide phosphate) is an orally active anticonvulsant with various endocrine-related side effects. Aminoglutethimide phosphate blocks multiple steroid hormone synthesis pathways by inhibiting several cytochrome P-450-dependent hydroxylases, such as aromatase, cholesterol side-chain cleavage enzyme, 11-hydroxylase, and 18-hydroxylase, with IC₅₀ values of 0.3, 3.5, 120, and 20 μM, respectively. Aminoglutethimide phosphate reduces cortisol levels. Aminoglutethimide phosphate can be used in research on Cushing's syndrome, breast cancer, and other conditions^[1][2][3][4]. In Vitro:Aminoglutethimide phosphate inhibits human placental microsomal aromatase by targeting cytochrome P-450, preventing the oxygen-dependent conversion of androgens to estrogens^[1].
Aminoglutethimide (0.05 mM; duration sufficient to produce complete steroidogenesis inhibition) phosphate completely inhibits steroidogenesis in monolayer cultures of functional adrenal tumour cells by directly targeting steroidogenic enzymes, without altering ACTH-induced cell morphology or glucose consumption^[4]. In Vivo:Aminoglutethimide (125-500 mg/kg/day; p.o.; once daily; 5 days) phosphate induces dose-dependent adrenal zona fasciculata cell damage including cytoplasmic vacuolation, single cell necrosis, excessive lipid accumulation, mitochondrial injury, and accelerated lysosomal degradation (mitophagy and lipophagy) in male Crlj:CD1(ICR) mice^[3].
Aminoglutethimide (8 days) phosphate exhibits goitrogenic activity and interferes with thyroid metabolism in intact rats on a low iodine diet, as evidenced by increased thyroid weight and reduced radio-iodine uptake^[4].
Aminoglutethimide phosphate induces thyromegaly, reduces thyroxine and di-iodotyrosine production, and increases thyroidal inorganic iodide levels in Rattus norvegicus^[4].
Aminoglutethimide phosphate inhibits adrenal steroid biosynthesis in rats and puppies, inducing adrenal hypertrophy, decreased corticosterone production, increased plasma ACTH, and characteristic cortical histological changes^[4].
Aminoglutethimide phosphate induces ovarian enlargement in intact rats and potential uterine enlargement in hypophysectomized rats^[4].
Aminoglutethimide (large doses) phosphate disrupts ovarian function, halts oestrous cycles, induces sterility, and reduces oestrogen-related uterine weight in intact female rats^[4].
Aminoglutethimide (10 mg/kg; i.v.) phosphate is active to inhibit cortisol secretion and block the steroidogenic response to ACTH in dogs^[4].