Recent advances in the development of melatonin MT(1) and MT(2) receptor agonists.

IMPORTANCE OF THE FIELD: Increasing clinical evidences suggest that melatonin receptor agonists can represent a novel therapeutic approach for the treatment of sleep disturbances and depression. A variety of studies also revealed a role of melatonin and its receptors in different patho-physiological conditions. Due to the multiple effects of this hormone, the design of new agents able to interact selectively with melatonin receptors has become an area of great interest during the last decade. AREAS COVERED IN THIS REVIEW: An extensive inspection of patents and scientific literature about MT(1) and MT(2) melatonin receptor agonists reported from 1999 to early 2010. WHAT THE READER WILL GAIN: A comprehensive review of structures recently claimed as melatonin receptor agonists and a broad overview of structure-activity relationships for these ligands. TAKE HOME MESSAGE: After 5 decades of research, the field of melatonin receptor agonists comprises a variety of chemical entities, belonging to structurally different classes. Patents filed since 1999 claim new melatonin receptor agonists, characterized either by improved pharmacokinetic or pharmacodynamic properties, compared to those of melatonin receptor agonists already approved for clinical uses. The results of preclinical studies on animal models show that melatonin receptor agonists can be considered promising agents for the treatment of CNS-related pathologies.