Dukes M, Edwards P N, Large M, Smith I K, Boyle T
Zeneca Pharmaceuticals, Alderly Park, Macclesfield, U.K.
J Steroid Biochem Mol Biol. 1996 Jul;58(4):439-45. doi: 10.1016/0960-0760(96)00064-7.
Anastrozole is a comparatively simple, achiral benzyltriazole derivative, 2,2'-[5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene]bis(2-++ +methylpropiononitrile), that inhibits human placental aromatase with an IC50 of 15 nM and elicits maximal activity in vivo in rats (inhibition of ovulation and androstenedione-induced uterine hypertrophy) and monkeys (lowering of plasma oestradiol) at 0.1 mg/kg p.o. At 30 times this dose, anastrozole does not elevate plasma 11-deoxycorticosterone in monkeys, and at 100 times this dose, does not affect plasma aldosterone levels or Na+/K+ excretion in rats, plasma K+ concentrations in dogs, or cause adrenal hypertrophy in rats or dogs. It therefore has no discernible effect on adrenocorticoid hormone synthesis in vivo at very large multiples of its maximally effective aromatase-inhibiting dose. At similar large multiples in rats it displays no oestrogenic, anti-oestrogenic, androgenic, anti-androgenic, progestogenic, glucocorticoid, antiglucocorticoid or mineralocorticoid activity. Anastrozole is thus a potent and highly selective aromatase inhibitor, with no intrinsic hormonal activities--a pharmacological profile particularly suitable for the treatment of breast cancer.
阿那曲唑是一种相对简单的、无手性的苄基三唑衍生物，即2,2'-[5-(1H-1,2,4-三唑-1-基甲基)-1,3-亚苯基]双(2-甲基丙腈)，它对人胎盘芳香化酶的抑制IC50为15 nM，在大鼠体内（抑制排卵和雄烯二酮诱导的子宫肥大）和猴子体内（降低血浆雌二醇水平），口服0.1 mg/kg时可产生最大活性。在该剂量的30倍时，阿那曲唑不会使猴子血浆11-脱氧皮质酮升高；在该剂量的100倍时，不会影响大鼠的血浆醛固酮水平或钠/钾排泄、狗的血浆钾浓度，也不会导致大鼠或狗的肾上腺肥大。因此，在其最大有效芳香化酶抑制剂量的很大倍数下，它对体内肾上腺皮质激素合成没有明显影响。在大鼠中，以类似的大倍数给药时，它没有显示出雌激素、抗雌激素、雄激素、抗雄激素、孕激素、糖皮质激素、抗糖皮质激素或盐皮质激素活性。因此，阿那曲唑是一种强效且高度选择性的芳香化酶抑制剂，没有内在激素活性——这一药理学特性特别适合用于治疗乳腺癌。
