Abstract：
Recently, the gamma-aminobutyric acid (GABA) system has come into focus for the treatment of anxiety, postpartum depression, and major depressive disorder. Endogenous 3α-reduced steroids such as allopregnanolone are potent positive allosteric modulators of GABAA receptors and have been known for decades. Current industry developments and first approvals by the U.S. food and drug administration (FDA) for the treatment of postpartum depression with exogenous analogues of these steroids represent a major step forward in the field. 3α-reduced steroids target both synaptic and extrasynaptic GABAA receptors, unlike benzodiazepines, which bind to synaptic receptors. The first FDA-approved 3α-reduced steroid for postpartum depression is brexanolone, an intravenous formulation of allopregnanolone. It has been shown to provide rapid relief of depressive symptoms. An orally available 3α-reduced steroid is zuranolone, which also received FDA approval in 2023 for the treatment of postpartum depression. Although a number of studies have been conducted, the efficacy data were not sufficient to achieve approval of zuranolone in major depressive disorder by the FDA in 2023. The most prominent side effects of these 3α-reduced steroids are somnolence, dizziness and headache. In addition to the issue of efficacy, it should be noted that current data limit the use of these compounds to two weeks. An alternative to exogenous 3α-reduced steroids may be the use of substances that induce endogenous neurosteroidogenesis, such as the translocator protein 18 kDa (TSPO) ligand etifoxine. TSPO has been extensively studied for its role in steroidogenesis, in addition to other functions such as anti-inflammatory and neuroregenerative properties. Currently, etifoxine is the only clinically available TSPO ligand in France for the treatment of anxiety disorders. Studies are underway to evaluate its antidepressant potential. Hopefully, neurosteroid research will lead to the development of fast-acting antidepressants.
摘要：
最近,γ-氨基丁酸（GABA）系统已成为治疗焦虑症的重点，产后抑郁症,和重度抑郁症.内源性3α-减少的类固醇如别孕烯醇酮是GABAA受体的有效正变构调节剂,并且已经已知数十年。当前的行业发展和美国食品和药物管理局（FDA）首次批准使用这些类固醇的外源性类似物治疗产后抑郁症代表了该领域的重要一步。3α减少的类固醇靶向突触和突触外GABAA受体，与苯二氮卓类药物不同，与突触受体结合。第一个FDA批准的用于产后抑郁症的3α减少类固醇是brexanolone，别孕烯醇酮的静脉注射制剂。它已被证明可以快速缓解抑郁症状。一种可口服的3α-减少类固醇是zuranolone，该药物还于2023年获得FDA批准用于治疗产后抑郁症。尽管已经进行了许多研究，这些疗效数据不足以在2023年获得FDA批准Zuranolone治疗重度抑郁症.这些3α减少的类固醇最突出的副作用是嗜睡，头晕头痛.除了功效问题，应该注意的是，目前的数据将这些化合物的使用限制在两周内。外源性3α减少类固醇的替代方法可能是使用诱导内源性神经类固醇生成的物质。例如转运蛋白18kDa(TSPO)配体依替福辛。TSPO在类固醇生成中的作用已被广泛研究，除了其他功能，如抗炎和神经再生特性。目前,依替福辛是法国唯一临床上可用于治疗焦虑症的TSPO配体。正在进行研究以评估其抗抑郁药的潜力。希望,神经类固醇研究将导致快速作用的抗抑郁药的发展。
