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精神疾病与氧化损伤:唑吡坦治疗的抗氧化作用已被揭示。

Psychiatric Disorders and Oxidative Injury: Antioxidant Effects of Zolpidem Therapy disclosed .

作者信息

Bortoli Marco, Dalla Tiezza Marco, Muraro Cecilia, Pavan Chiara, Ribaudo Giovanni, Rodighiero Anna, Tubaro Cristina, Zagotto Giuseppe, Orian Laura

机构信息

Dipartimento di Scienze Chimiche, Università degli Studi di Padova, Via Marzolo 1, 35131 Padova, Italy.

Dipartimento di Medicina, Università degli Studi di Padova, Via Giustiniani 2, 35128 Padova, Italy.

出版信息

Comput Struct Biotechnol J. 2019 Feb 7;17:311-318. doi: 10.1016/j.csbj.2019.02.004. eCollection 2019.

Abstract

Zolpidem (,-Dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-]pyridin-3-yl]acetamide) is a well-known drug for the treatment of sleeping disorders. Recent literature reports on positive effects of zolpidem therapy on improving renal damage after cisplatin and on reducing akinesia without sleep induction. This has been ascribed to the antioxidant and neuroprotective capacity of this molecule, and tentatively explained according to a generic structural similarity between zolpidem and melatonin. In this work, we investigate the antioxidant potential of zolpidem as scavenger of five ROSs, acting via hydrogen atom transfer (HAT) mechanism; computational methodologies based on density functional theory are employed. For completeness, the analysis is extended to six metabolites. Thermodynamic and kinetic results disclose that indeed zolpidem is an efficient radical scavenger, similarly to melatonin and Trolox, supporting the biomedical evidence that the antioxidant potential of zolpidem therapy may have a beneficial effect against oxidative injury, which is emerging as an important etiopathogenesis in numerous severe diseases, including psychiatric disorders.

摘要

唑吡坦(,-二甲基-2-[6-甲基-2-(4-甲基苯基)咪唑并[1,2-]吡啶-3-基]乙酰胺)是一种治疗睡眠障碍的知名药物。最近的文献报道了唑吡坦治疗对改善顺铂后肾损伤以及在不诱导睡眠的情况下减轻运动不能的积极作用。这归因于该分子的抗氧化和神经保护能力,并根据唑吡坦与褪黑素之间的一般结构相似性进行了初步解释。在这项工作中,我们研究了唑吡坦作为五种活性氧清除剂的抗氧化潜力,其通过氢原子转移(HAT)机制起作用;采用了基于密度泛函理论的计算方法。为了全面起见,分析扩展到了六种代谢物。热力学和动力学结果表明,唑吡坦确实是一种有效的自由基清除剂,类似于褪黑素和曲洛昔康,支持了生物医学证据,即唑吡坦治疗的抗氧化潜力可能对氧化损伤具有有益作用,氧化损伤正成为包括精神疾病在内的许多严重疾病的重要发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54c/6396081/20c83340a44b/ga1.jpg

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