Due to high oxygen consumption, the brain is particularly vulnerable to oxidative stress, which is considered an important element in the etiopathogenesis of several mental disorders, including schizophrenia, depression and dependencies. Despite the fact that it is not established yet whether oxidative stress is a cause or a consequence of clinic manifestations, the intake of antioxidant supplements in combination with the psychotropic therapy constitutes a valuable solution in patients’ treatment. Anyway, some drugs possess antioxidant capacity themselves and this aspect is discussed in this review, focusing on antipsychotics and antidepressants. In the context of a collection of clinical observations, in vitro and in vivo results are critically reported, often highlighting controversial aspects. Finally, a new challenge is discussed, i.e., the possibility of assessing in silico the antioxidant potential of these drugs, exploiting computational chemistry methodologies and machine learning. Despite the physiological environment being incredibly complex and the detection of meaningful oxidative stress biomarkers being all but an easy task, a rigorous and systematic analysis of the structural and reactivity properties of antioxidant drugs seems to be a promising route to better interpret therapeutic outcomes and provide elements for the rational design of novel drugs.

中文翻译：

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精神药物的抗氧化潜力：从临床证据到体外和体内评估以及计算机分子设计的新挑战。


由于高耗氧量，大脑特别容易受到氧化应激的影响，氧化应激被认为是多种精神疾病发病机制的重要因素，包括精神分裂症、抑郁症和依赖性。尽管目前尚不清楚氧化应激是临床表现的原因还是结果，但摄入抗氧化剂补充剂与精神药物治疗相结合构成了患者治疗中的一个有价值的解决方案。无论如何，一些药物本身具有抗氧化能力，本综述讨论了这一方面，重点关注抗精神病药和抗抑郁药。在收集临床观察的背景下，体外和体内结果得到了严格的报告，通常突出了有争议的方面。最后，讨论了一个新的挑战，即利用计算化学方法和机器学习在计算机上评估这些药物的抗氧化潜力的可能性。尽管生理环境极其复杂，并且检测有意义的氧化应激生物标志物几乎是一项简单的任务，但对抗氧化药物的结构和反应特性进行严格和系统的分析似乎是更好地解释治疗结果并提供要素的一条有前途的途径。以便合理设计新药。