Melatonin receptor ligands

Abstract

The hormone melatonin is released following a circardian rhythm with highest levels during the subjective night. It regulates a variety of physiological and neuroendocrine functions through activation of G-protein-coupled membrane receptors in target tissues. The lipophilic structure of melatonin also suggests an intracellular function and the nuclear receptor RZR/ROR was associated with a direct gene regulatory action of the hormone. In recent years, many putative ligands for membrane bound melatonin receptors have been synthesised, which represent indole derivatives or contain bioisosteric moieties and have structural elements identical or similar to the functional groups in the melatonin molecule. Two mammalian melatonin receptors (mt₁ and MT₂) with 60% homology at amino acid level have been cloned and simplify the search for selective agonists and antagonists. Recently, several ligands with a considerable selectivity for the MT₂ receptor have been identified. In addition, many melatonergic compounds have been patented and claimed to be useful for the treatment of depression, sleep disorders, disturbances 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 nuclear receptor RZR/ROR. These compounds exhibit potent anti-arthritic activity and may also have a therapeutic potential against several types of cancer.

• cancer
• melatonin
• melatonin membrane receptors
• RZR/ROR
• sleep disorders