Pineal hormone melatonin is widely used in the treatment of disorders of circadian rhythms. The presence of melatonin receptors in various animal tissues motivates the use of this hormone in some other diseases. For this reason, in recent years investigators continued the search for synthetic analogues of melatonin which are metabolically stable and selective to receptors. This review includes recent information about the most famous melatonin analogues, their structure, properties, and physiological features of the interaction with melatonin receptors. 1. Introduction Almost since its opening in the mid-20th century epiphyseal hormone melatonin is seen as a valuable pharmacological agent. The results of the subsequent thorough and comprehensive study of the biochemical and physiological effects of melatonin have only confirmed this view. The positive results of the use of melatonin were obtained for the treatment of insomnia, circadian rhythm disorders associated with shift work, the change of time zones, and seasonal disorders [1–3]. The expediency of the use of melatonin is shown in the treatment of cardiovascular diseases, cancer, and other diseases [4, 5]. However, the widespread introduction of the drug in clinical practice has not been observed. Experts believe that one of the limiting factors is the short half-life of melatonin. In recent years, two approaches to this problem are emerged. The first way is connected with the improvement of the pharmacokinetics due to the creation of medicinal forms of prolonged action. For example, the company Neurim Pharmaceuticals has produced drug called Circadin, mimicking physiological profile of epiphyseal hormone secretion. The second path involves the creation of more stable agonists, which also could selectively bind with a specific type of melatonin receptor. At present, this area is considered to be more promising. This topic is the focus of this review. 2. Melatonin 2.1. Structure and Biological Function of Melatonin Melatonin (N-acetyl-5-methoxytryptamine) is a heterocyclic compound, derivative of indole (Figure 1). Figure 1: Structure of melatonin. In mammals, melatonin controls the set of physiological functions. It participates in the formation of circadian and seasonal rhythms [6–8], behavioral reactions [9, 10], and adaptation [11, 12]. It plays an important role in the regulation of reproductive function [13], the cardiovascular system [14, 15], immune reactions [16, 17], the restriction of the processes of cell proliferation, and tumor growth [18, 19]. Accumulated experimental data evidently
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