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首页> 外文期刊>Drug news & perspectives >The role of ML-23 and other melatonin analogues in the treatment and management of Parkinson's disease.
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The role of ML-23 and other melatonin analogues in the treatment and management of Parkinson's disease.

机译：ML-23和其他褪黑激素类似物在帕金森氏病治疗和管理中的作用。

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Contemporary theory regarding the cause and treatment of neuropsychiatric disease strongly suggests that as the human body ages it gradually loses the intrinsic safeguards that protect it from oxidative damage. Melatonin is one hormone that serves this function in that it possesses antioxidative properties in the mammalian body and brain. Melatonin has been shown to prevent the progressive degeneration produced by neurotoxins employed in experimental models to mimic the degenerative events in various neuropsychiatric disease states. There are an abundance of models for numerous disease states demonstrating that melatonin can inhibit oxidative stress and by such a mechanism it is presumed to exert a therapeutic effect. While a similar scenario has been revealed with in vitro work relating specifically to Parkinson's disease, clinical work with melatonin in this disorder demonstrates that it is devoid of any remarkable therapeutic effects. More recent preclinical and clinical work has reliably demonstrated that melatonin in fact may be without therapeutic efficacy and may even worsen the condition. On this pretense, attempts to reduce the bioavailability of melatonin using a melatonin receptor antagonist have been found to completely restore behavioral and regulatory function in the presence of chronically reduced levels of dopamine, without producing side effects commonly seen with traditional dopamine replacement therapy. The unavoidable conclusion from this work suggests that within the dynamic framework of the mammalian brain, hormones may play a duel, and possibly ambivalent, role in homeostasis and in the etiology of disease. Such a position requires a reevaluation of the etiology, the role of dopamine, the neurochemical characteristics of Parkinson's disease and the validity of the models employed to study this and other neuropsychiatric disorders.
机译：关于神经精神疾病的病因和治疗的当代理论有力地表明，随着人体年龄的增长，它逐渐失去了保护其免受氧化损伤的内在保障。褪黑激素是一种具有这种功能的激素，因为它在哺乳动物的身体和大脑中具有抗氧化特性。褪黑素已显示出可以预防由在实验模型中模仿多种神经精神疾病状态的退化事件的神经毒素产生的进行性退化。有大量针对多种疾病状态的模型，证明褪黑激素可以抑制氧化应激，并且据推测，通过这种机制，褪黑激素可以发挥治疗作用。尽管专门针对帕金森氏病的体外研究发现了类似的情况，但褪黑激素在这种疾病中的临床研究表明它没有任何显着的治疗作用。最近的临床前和临床工作已经可靠地证明，褪黑激素实际上可能没有治疗功效，甚至可能使病情恶化。以此为借口，已经发现尝试使用褪黑激素受体拮抗剂降低褪黑激素的生物利用度，可以在长期降低多巴胺水平的情况下完全恢复行为和调节功能，而不会产生传统多巴胺替代疗法常见的副作用。这项工作不可避免的结论表明，在哺乳动物大脑的动态框架内，激素可能在体内平衡和疾病病因中起着双重作用，甚至可能起矛盾作用。这样的职位需要重新评估病因，多巴胺的作用，帕金森氏病的神经化学特征以及用于研究该疾病和其他神经精神疾病的模型的有效性。

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