School of Pharmacy, Hangzhou Medical College (Zhejiang Academy of Medical Sciences), Hangzhou, Zhejiang, People's Republic of China; Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou, Zhejiang, People's Republic of China.
Pharmacol Res. 2021 Jul;169:105682. doi: 10.1016/j.phrs.2021.105682. Epub 2021 May 18.
The neuroactive steroid allopregnanolone (ALLO) is an endogenous positive allosteric modulator of GABA type A receptor (GABAR), and the down-regulation of its biosynthesis have been attributed to the development of mood disorders, such as depression, anxiety and post-traumatic stress disorder (PTSD). ALLO mediated depression/anxiety involves GABAergic mechanisms and appears to be related to brain-derived neurotrophic factor (BDNF), dopamine receptor, glutamate neurotransmission, and Ca channel. In the clinical, brexanolone, as a newly developed intravenous ALLO preparation, has been approved for the treatment of postpartum depression (PPD). In addition, traditional antidepressants such as selective serotonin reuptake inhibitor (SSRI) could reverse ALLO decline. Recently, the translocation protein (TSPO, 18 kDa), which involves in the speed-limiting step of ALLO synthesis, and ALLO derivatization have been identified as new directions for antidepressant therapy. This review provides an overview of ALLO researches in animal model and patients, discusses its role in the development and treatment of depression/anxiety, and directs its therapeutic potential in future.
神经活性甾体化合物孕烷二醇（ALLO）是 GABA 型 A 受体（GABAR）的内源性正变构调节剂，其生物合成的下调与心境障碍（如抑郁症、焦虑症和创伤后应激障碍（PTSD））的发展有关。ALLO 介导的抑郁/焦虑涉及 GABA 能机制，似乎与脑源性神经营养因子（BDNF）、多巴胺受体、谷氨酸能神经传递和钙通道有关。在临床中，作为一种新开发的静脉内 ALLO 制剂，brexanolone 已被批准用于治疗产后抑郁症（PPD）。此外，传统的抗抑郁药，如选择性 5-羟色胺再摄取抑制剂（SSRI），可以逆转 ALLO 的下降。最近，转运蛋白（TSPO，18 kDa），其涉及 ALLO 合成的限速步骤，和 ALLO 衍生化已被确定为抗抑郁治疗的新方向。本文综述了 ALLO 在动物模型和患者中的研究，讨论了其在抑郁/焦虑发展和治疗中的作用，并指导了其在未来的治疗潜力。
