Prokai-Tatrai Katalin, Nguyen Vien, Prokai Laszlo
Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
J Pharm Drug Res. 2016;1(1):1-6. Epub 2016 May 15.
In this exploratory study, we performed an evaluation of non-feminizing estrogens as lead compounds for the safe treatment of menopausal symptoms. Despite confirming an enhancement of antioxidant potency as a consequence of increased lipophilicity of the prototype structures, our analyses have revealed serious shortcomings regarding pharmaceutically important properties and drug-likeness. In addition, our assessment in an animal model of estrogen deprivation has confirmed that genomic mechanisms are required for the alleviation of menopause-associated depression. Therefore, non-feminizing estrogens are not suitable to fulfill their implicated premise to address unmet needs to treat neurological and psychiatric conditions associated with estrogen deprivation of the brain.
在这项探索性研究中，我们对非女性化雌激素作为安全治疗更年期症状的先导化合物进行了评估。尽管证实了原型结构亲脂性增加导致抗氧化能力增强，但我们的分析揭示了其在药学重要性质和类药性质方面存在严重缺陷。此外，我们在雌激素缺乏动物模型中的评估证实，缓解更年期相关抑郁症需要基因组机制。因此，非女性化雌激素不适合实现其隐含的前提，即满足治疗与大脑雌激素缺乏相关的神经和精神疾病这一未满足的需求。
