Melatonin receptor ligands

The hormone melatonin is released following a circardian rhythm with highes t levels during the subjective night. It regulates a variety of physiologic al and neuroendocrine functions through activation of G-protein-coupled mem brane receptors in target tissues; The lipophilic structure of melatonin al so suggests an intracellular function and the nuclear receptor RZR/ROR was associated with a direct gene regulatory action of the hormone. In recent y ears, many putative ligands for membrane bound melatonin receptors have bee n synthesised, which represent indole derivatives or contain bioisosteric m oieties and have structural elements identical or similar to the functional groups in the melatonin molecule. Two mammalian melatonin receptors (mt(1) and MT2) with 60% homology at amino acid level have been cloned and simpli fy the search for selective agonists and antagonists. Recently, several lig ands with a considerable selectivity for the MT2 receptor have been identif ied. In addition, many melatonergic compounds have been patented and claime d to be useful for the treatment of depression, sleep disorders, disturbanc es of the circadian rhythm, anxiety disorders, cardiovascular diseases and cancer. Thiazolidinedione derivatives have been identified as structurally distinct but functional melatonin analogues that seem to act via the nuclea r receptor RZR/ROR. These compounds exhibit potent anti-arthritic activity and may also have a therapeutic potential against several types of cancer.