Reiter Russel J, Tan Dun-Xian, Sainz Rosa M, Mayo Juan C, Lopez-Burillo Silvia
University of Texas Health Science Center, Department of Cellular and Structural Biology, MC 7762, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
J Pharm Pharmacol. 2002 Oct;54(10):1299-321. doi: 10.1211/002235702760345374.
Melatonin (N-acetyl-5-methoxytryptamine) is a molecule with a very wide phylogenetic distribution from plants to man. In vertebrates, melatonin was initially thought to be exclusively of pineal origin recent studies have shown, however, that melatonin synthesis may occur in a variety of cells and organs. The concentration of melatonin within body fluids and subcellular compartments varies widely, with blood levels of the indole being lower than those at many other sites. Thus, when defining what constitutes a physiological level of melatonin, it must be defined relative to a specific compartment. Melatonin has been shown to have a variety of functions, and research in the last decade has proven the indole to be both a direct free radical scavenger and indirect antioxidant. Because of these actions, and possibly others that remain to be defined, melatonin has been shown to reduce the toxicity and increase the efficacy of a large number of drugs whose side effects are well documented. Herein, we summarize the beneficial effects of melatonin when combined with the following drugs: doxorubicin, cisplatin, epirubicin, cytarabine, bleomycin, gentamicin, ciclosporin, indometacin, acetylsalicylic acid, ranitidine, omeprazole, isoniazid, iron and erythropoietin, phenobarbital, carbamazepine, haloperidol, caposide-50, morphine, cyclophosphamide and L-cysteine. While the majority of these studies were conducted using animals, a number of the investigations also used man. Considering the low toxicity of melatonin and its ability to reduce the side effects and increase the efficacy of these drugs, its use as a combination therapy with these agents seems important and worthy of pursuit.
褪黑素（N-乙酰-5-甲氧基色胺）是一种在从植物到人类的生物进化过程中广泛分布的分子。在脊椎动物中，褪黑素最初被认为仅由松果体产生，然而最近的研究表明，褪黑素的合成可能发生在多种细胞和器官中。体液和亚细胞区室中褪黑素的浓度差异很大，吲哚在血液中的水平低于许多其他部位。因此，在定义什么构成褪黑素的生理水平时，必须相对于特定的区室来定义。褪黑素已被证明具有多种功能，过去十年的研究证明这种吲哚既是一种直接的自由基清除剂，也是一种间接的抗氧化剂。由于这些作用，以及可能还有其他有待确定的作用，褪黑素已被证明可以降低大量副作用已被充分记录的药物的毒性并提高其疗效。在此，我们总结了褪黑素与以下药物联合使用时的有益作用：阿霉素、顺铂、表柔比星、阿糖胞苷、博来霉素、庆大霉素、环孢素、吲哚美辛、乙酰水杨酸、雷尼替丁、奥美拉唑、异烟肼、铁和促红细胞生成素、苯巴比妥、卡马西平、氟哌啶醇、卡泊苷-50、吗啡、环磷酰胺和L-半胱氨酸。虽然这些研究大多是在动物身上进行的，但也有一些研究使用了人类。考虑到褪黑素的低毒性及其降低这些药物副作用和提高疗效的能力，将其作为这些药物的联合治疗手段似乎很重要且值得探索。
