New Radioligands for Describing the Molecular Pharmacology of MT(1) and MT(2) Melatonin Receptors

Melatonin receptors have been studied for several decades. The low expression of the receptors in tissues led the scientific community to find a substitute for the natural hormone melatonin, the agonist 2-[(125)I]-iodomelatonin. Using the agonist, several hundreds of studies were conducted, including the discovery of agonists and antagonists for the receptors and minute details about their molecular behavior. Recently, we attempted to expand the panel of radioligands available for studying the melatonin receptors by using the newly discovered compounds SD6, DIV880, and S70254. These compounds were characterized for their affinities to the hMT(1) and hMT(2) recombinant receptors and their functionality in the classical GTPγS system. SD6 is a full agonist, equilibrated between the receptor isoforms, whereas S70254 and DIV880 are only partial MT(2) agonists, with K(i) in the low nanomolar range while they have no affinity to MT(1) receptors. These new tools will hopefully allow for additions to the current body of information on the native localization of the receptor isoforms in tissues.