Drugs that inhibit aromatase: AMINOGLUTETHIMIDE, ANASTROZOLE, LETROZOLE, EXEMESTANE
Mechanism
Aromatase inhibitors target the conversion of testosterone and androstenedione to estradiol and estrone, respectively. Steroid analogues, such as EXEMESTANE, IRREVERSIBLY inhibit aromatase, while non-steroidal drugs (AMINOGLUTETHIMIDE, ANASTROZOLE and LETROZOLE) compete REVERSIBLY for the androstenedione binding site. AMINOGLUTETHIMIDE also blocks conversion of cholesterol to pregnenolone, decreasing concentrations of adrenal gluco- and mineralocorticoids as well as sex hormones. |
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can be classified as first generation (AMINOGLUTETHIMIDE) or third generation (EXEMESTANE, ANASTROZOLE, LETROZOLE)
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overall result is block of estrogen synthesis (90-98% for 3rd generation drugs), with a resulting decrease in estrogen levels in the circulation
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steroidal derivatives of androstenedione (EXEMESTANE) bind IRREVERSIBLY to the androgen binding site following aromatization
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non-steroidal drugs are competitive inhibitors (i.e., REVERSIBLE) of androstenedione for the binding site on the cytochrome P450 part of the enzyme complex - they are not altered by the enzyme
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in addition to its weak inhibition of aromatase, AMINOGLUTETHIMIDE prevents conversion of cholesterol to pregnenolone à it blocks synthesis of all steroids (cortisol, testosterone, progesterone)