Drug nameAminoglutethimide
DescriptionAn aromatase inhibitor that produces a state of medical adrenalectomy by blocking the production of adrenal steroids. It also blocks the conversion of androgens to estrogens. Aminoglutethimide has been used in the treatment of advanced breast and prostate cancer. It was formerly used for its weak anticonvulsant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p454)
DrugBankPrimary Accession Number: DB00357
TypeApproved, Small Molecule
IndicationFor the suppression of adrenal function in selected patients with Cushing`s syndrome, malignant neoplasm of the female breast, and carcinoma in situ of the breast.
Mechanism of ActionAminoglutethimide reduces the production of D5-pregnenolone and blocks several other steps in steroid synthesis, including the C-11, C-18, and C-21 hydroxylations and the hydroxylations required for the aromatization of androgens to estrogens, mediated through the binding of aminoglutethimide to cytochrome P-450 complexes. A decrease in adrenal secretion of cortisol is followed by an increased secretion of pituitary adrenocorticotropic hormone (ACTH), which will overcome the blockade of adrenocortical steroid synthesis by aminoglutethimide. The compensatory increase in ACTH secretion can be suppressed by the simultaneous administration of hydrocortisone. Since aminoglutethimide increases the rate of metabolism of dexamethasone but not that of hydrocortisone, the latter is preferred as the adrenal glucocorticoid replacement. Although aminoglutethimide inhibits the synthesis of thyroxine by the thyroid gland, the compensatory increase in thyroid-stimulating hormone (TSH) is frequently of sufficient magnitude to overcome the inhibition of thyroid synthesis due to aminoglutethimide. In spite of an increase in TSH, aminoglutethimide has not been associated with increased prolactin secretion.
AbsorptionRapidly and completely absorbed from gastrointestinal tract. The bioavailability of tablets is equivalent to equal doses given as a solution.
ToxicityOral LD50s (mg/kg): rats, 1800; dogs, >100. Intravenous LD50s (mg/kg): rats, 156; dogs, >100. Symptoms of overdose include respiratory depression, hypoventilation, hypotension, hypovolemic shock due to dehydration, somnolence, lethargy, coma, ataxia, dizziness, fatigue, nausea, and vomitin
Protein Binding21-25%
KEGGdrug: D00574 / compound: C07617
PubChemcompound: 2145 / substance: 9819
Metabolizing Enzymes
Cytochrome P450 19A1CYP19A11588CP19A_HUMANrs61203654 rs61317221 rs28757184 rs60308277 rs2304461 rs59359360 rs700519 rs58282176 rs2236722 rs700518 rs56658716 rs35900050 rs34896264 rs28757183 rs17853490 rs11540804 rs2304462 rs1803154
FilesDB00357.mol | DB00357_2003-05-01.pdf | pdb_993852831309-0.pdb | sdf_9386684714996-0(2).sdf |

© 2010-2020 All rights reserved. King Abdullah University of Science and Technology, All rights reserved