el Etreby M F, Nishino Y, Habenicht U F, Henderson D
Research Laboratories of Schering AG, Berlin, Germany.
J Androl. 1991 Nov-Dec;12(6):403-14.
Atamestane is a new, competitive, and irreversible inhibitor of estrogen biosynthesis. Its pharmacologic action has been evaluated in mice, rats, rabbits, dogs, monkeys, and humans. In rats, atamestane leads to a decrease of pregnant mare serum gonadotropin-stimulated ovarian estrogen production, and inhibits androstenedione-induced estrogenic effects such as uterine growth and abortion. In all species tested, atamestane lacks other intrinsic hormonal or antihormonal activities, and shows no inhibition of other cytochrome P450-dependent enzymes of adrenal steroidogenesis. However, it inhibits estrogen-related negative feedback. The extent and consequences of the induced counterregulation of the pituitary-hypothalamic axis show major sex- and species-specific differences. Atamestane is highly effective in inhibiting estrogen-induced hyperplastic changes in the fibromuscular stroma of the prostate in androstenedione-treated dogs and monkeys. In male volunteers and patients with benign prostatic hyperplasia (BPH), atamestane induces an expected reduction of serum (and BPH tissue) estrogen concentrations without significant changes in androgen levels. In conclusion, all available results indicate that atamestane is a selective (no inhibition of adrenal function), pure (no endocrine side effects), and highly effective steroidal aromatase inhibitor, with an excellent safety profile. Based on the discussion of its clinical potential, atamestane seems to be a promising compound for the management of BPH.
阿那曲唑是一种新型、竞争性且不可逆的雌激素生物合成抑制剂。已在小鼠、大鼠、兔子、狗、猴子和人类中评估了其药理作用。在大鼠中，阿那曲唑可导致孕马血清促性腺激素刺激的卵巢雌激素生成减少，并抑制雄烯二酮诱导的雌激素效应，如子宫生长和流产。在所有测试物种中，阿那曲唑缺乏其他内在激素或抗激素活性，并且对肾上腺类固醇生成的其他细胞色素P450依赖性酶无抑制作用。然而，它抑制雌激素相关的负反馈。垂体-下丘脑轴诱导的反调节的程度和后果显示出主要的性别和物种特异性差异。阿那曲唑在抑制雄烯二酮处理的狗和猴子前列腺纤维肌基质中雌激素诱导的增生性变化方面非常有效。在男性志愿者和良性前列腺增生（BPH）患者中，阿那曲唑可使血清（和BPH组织）雌激素浓度预期降低，而雄激素水平无明显变化。总之，所有现有结果表明，阿那曲唑是一种选择性（不抑制肾上腺功能）、纯（无内分泌副作用）且高效的甾体芳香化酶抑制剂，具有出色的安全性。基于对其临床潜力的讨论，阿那曲唑似乎是一种有前途的治疗BPH的化合物。
