Atamestane, a new aromatase inhibitor for the management of benign prostatic hyperplasia.
Atamestane, a new aromatase inhibitor for the management of benign prostatic hyperplasia.
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Atamestane，一种用于治疗良性前列腺增生的新型芳香酶抑制剂。
DOI：
10.1002/j.1939-4640.1991.tb00283.x
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发表时间：
1991
影响因子：
--
通讯作者：
David Henderson
中科院分区：
文献类型：
--
作者：
M. F. Etreby;Yukishige Nishino;U. Habenicht;David Henderson
阿他美坦是一种新的、竞争性的、不可逆的雌激素生物合成抑制剂。其药理作用已在小鼠、大鼠、家兔、狗、猴和人身上进行了评价。在大鼠中，阿美司坦导致妊娠母马血清促性腺激素刺激的卵巢雌激素产生减少，并抑制雄烯二酮诱导的雌激素效应，如子宫生长和流产。在所有被测试的物种中，阿美斯坦缺乏其他内在激素或抗激素活性，并且对其他依赖于肾上腺甾体生成的细胞色素p450酶没有抑制作用。然而，它抑制雌激素相关的负面反馈。诱导的垂体-下丘脑轴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。在雄烯二酮治疗的狗和猴子中，阿他美坦对抑制雌激素诱导的前列腺纤维肌间质增生变化非常有效。在男性志愿者和良性前列腺增生（BPH）患者中，阿美斯坦诱导血清（和BPH组织）雌激素浓度的预期降低，而雄激素水平没有显著变化。总之，所有可用的结果表明，阿他美坦是一种选择性（无肾上腺功能抑制）、纯性（无内分泌副作用）、高效的甾体芳香酶抑制剂，具有良好的安全性。基于对其临床潜力的讨论，阿他美坦似乎是一种治疗前列腺增生的有前途的化合物。
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.
人类前列腺中的雌激素受体：多个结合位点的证据。
DOI：
10.1210/jcem-57-1-166
发表时间：
1983
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Ekman,P;Barrack,ER;Greene,GL;Jensen,EV;Walsh,PC
通讯作者：
Walsh,PC