Hardeland Rüdiger
Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, 37073 Göttingen, Germany.
Diseases. 2021 Mar 9;9(1):18. doi: 10.3390/diseases9010018.
Melatonin has been used preclinically and clinically for different purposes. Some applications are related to readjustment of circadian oscillators, others use doses that exceed the saturation of melatonin receptors MT and MT and are unsuitable for chronobiological purposes. Conditions are outlined for appropriately applying melatonin as a chronobiotic or for protective actions at elevated levels. Circadian readjustments require doses in the lower mg range, according to receptor affinities. However, this needs consideration of the phase response curve, which contains a silent zone, a delay part, a transition point and an advance part. Notably, the dim light melatonin onset (DLMO) is found in the silent zone. In this specific phase, melatonin can induce sleep onset, but does not shift the circadian master clock. Although sleep onset is also under circadian control, sleep and circadian susceptibility are dissociated at this point. Other limits of soporific effects concern dose, duration of action and poor individual responses. The use of high melatonin doses, up to several hundred mg, for purposes of antioxidative and anti-inflammatory protection, especially in sepsis and viral diseases, have to be seen in the context of melatonin's tissue levels, its formation in mitochondria, and detoxification of free radicals.
褪黑素已在临床前和临床中用于不同目的。一些应用与昼夜节律振荡器的重新调整有关，其他应用使用的剂量超过了褪黑素受体MT1和MT2的饱和剂量，不适用于时间生物学目的。文中概述了将褪黑素作为时间生物制剂适当应用或在较高水平下发挥保护作用的条件。根据受体亲和力，昼夜节律调整需要较低毫克范围内的剂量。然而，这需要考虑相位响应曲线，该曲线包含一个静息区、一个延迟部分、一个转折点和一个提前部分。值得注意的是，暗光褪黑素起始（DLMO）出现在静息区内。在这个特定阶段，褪黑素可以诱导睡眠开始，但不会使昼夜节律主时钟发生偏移。虽然睡眠开始也受昼夜节律控制，但此时睡眠和昼夜节律易感性是分离的。催眠作用的其他局限性涉及剂量、作用持续时间和个体反应不佳。使用高达数百毫克的高剂量褪黑素用于抗氧化和抗炎保护，特别是在败血症和病毒疾病中，必须结合褪黑素的组织水平、其在线粒体中的形成以及自由基的解毒来考虑。
