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Neurosteroids as novel antidepressants and anxiolytics: GABA-A receptors and beyond.
Neurobiology of Stress ( IF 5 ) Pub Date : 2019-09-27 , DOI: 10.1016/j.ynstr.2019.100196
Charles F Zorumski 1, 2, 3 , Steven M Paul 1, 3, 4 , Douglas F Covey 1, 3, 5 , Steven Mennerick 1, 2, 3
Affiliation  

The recent FDA approval of the neurosteroid, brexanolone (allopregnanolone), as a treatment for women with postpartum depression, and successful trials of a related neuroactive steroid, SGE-217, for men and women with major depressive disorder offer the hope of a new era in treating mood and anxiety disorders based on the potential of neurosteroids as modulators of brain function. This review considers potential mechanisms contributing to antidepressant and anxiolytic effects of allopregnanolone and other GABAergic neurosteroids focusing on their actions as positive allosteric modulators of GABAA receptors. We also consider their roles as endogenous “stress” modulators and possible additional mechanisms contributing to their therapeutic effects. We argue that further understanding of the molecular, cellular, network and psychiatric effects of neurosteroids offers the hope of further advances in the treatment of mood and anxiety disorders.



中文翻译:

神经类固醇作为新型抗抑郁药和抗焦虑药:GABA-A 受体及其他。

最近 FDA 批准神经类固醇 brexanolone(allopregnanolone)用于治疗女性产后抑郁症,以及相关神经活性类固醇 SGE-217 针对患有重度抑郁症的男性和女性的成功试验带来了新时代的希望基于神经类固醇作为大脑功能调节剂的潜力来治疗情绪和焦虑症。本综述考虑了四氢孕酮和其他 GABA 能神经类固醇的抗抑郁和抗焦虑作用的潜在机制,重点关注它们作为 GABA A受体的正变构调节剂的作用。我们还考虑它们作为内源性“压力”调节剂的作用以及有助于其治疗效果的可能的其他机制。我们认为,对神经类固醇的分子、细胞、网络和精神效应的进一步了解为情绪和焦虑症的治疗取得进一步进展带来了希望。

更新日期:2019-09-27
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