Carocci Alessia, Catalano Alessia, Sinicropi Maria Stefania
Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Bari, Italy.
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Cosenza, Italy.
Clin Pharmacol. 2014 Sep 18;6:127-37. doi: 10.2147/CPAA.S36600. eCollection 2014.
Melatonin (N-acetyl-5-methoxytryptamine) is widely known as "the darkness hormone". It is a major chronobiological regulator involved in circadian phasing and sleep-wake cycle in humans. Numerous other functions, including cyto/neuroprotection, immune modulation, and energy metabolism have been ascribed to melatonin. A variety of studies have revealed a role for melatonin and its receptors in different pathophysiological conditions. However, the suitability of melatonin as a drug is limited because of its short half-life, poor oral bioavailability, and ubiquitous action. Due to the therapeutic potential of melatonin in a wide variety of clinical conditions, the development of new agents able to interact selectively with melatonin receptors has become an area of great interest during the last decade. Therefore, the field of melatonergic receptor agonists comprises a great number of structurally different chemical entities, which range from indolic to nonindolic compounds. Melatonergic agonists are suitable for sleep disturbances, neuropsychiatric disorders related to circadian dysphasing, and metabolic diseases associated with insulin resistance. The results of preclinical studies on animal models show that melatonin receptor agonists can be considered promising agents for the treatment of central nervous system-related pathologies. An overview of recent advances in the field of investigational melatonergic drugs will be presented in this review.
褪黑素（N-乙酰-5-甲氧基色胺）广为人知，被称为“黑暗荷尔蒙”。它是一种主要的生物钟调节剂，参与人体的昼夜节律和睡眠-觉醒周期。褪黑素还具有许多其他功能，包括细胞/神经保护、免疫调节和能量代谢。各种研究揭示了褪黑素及其受体在不同病理生理状况中的作用。然而，由于褪黑素半衰期短、口服生物利用度低以及作用广泛，其作为药物的适用性受到限制。鉴于褪黑素在多种临床状况中的治疗潜力，在过去十年中，开发能够与褪黑素受体选择性相互作用的新型药物已成为一个备受关注的领域。因此，褪黑素能受体激动剂领域包含大量结构不同的化学实体，从吲哚类化合物到非吲哚类化合物都有。褪黑素能激动剂适用于睡眠障碍、与昼夜节律失调相关的神经精神疾病以及与胰岛素抵抗相关的代谢疾病。对动物模型的临床前研究结果表明，褪黑素受体激动剂可被视为治疗中枢神经系统相关病症的有前景的药物。本综述将概述研究性褪黑素能药物领域的最新进展。
