New selective ligands of human cloned melatonin MT1 and MT2 receptors

Naunyn Schmiedebergs Arch Pharmacol. 2003 Jun;367(6):553-61. doi: 10.1007/s00210-003-0751-2. Epub 2003 May 23.


Melatonin has a key role in the circadian rhythm relay to periphery organs. Melatonin exerts its multiple roles mainly through two seven transmembrane domain, G-coupled receptors, namely MT1 or MT2 receptors. A pharmacological characterization of these human cloned melatonin hMT1 and hMT2 receptors stably expressed in HEK-293 or CHO cells is presented using a 2-[125I]-iodo-melatonin binding assay and a [35S]-GTPgammaS functional assay. Both reference compounds and new chemically diverse ligands were evaluated. Binding affinities at each receptor were found to be comparable on either HEK-293 or CHO cell membranes. Novel non-selective or selective hMT1 and hMT2 ligands are described. The [35S]-GTPgammaS functional assay was used to define the functional activity of these compounds which included partial, full agonist and/or antagonist activity. None of the compounds acted as an inverse agonist. We report new types of selective antagonists, such as S 25567 and S 26131 for MT1 and S 24601 for MT2. These studies brought other new molecular tools such as the selective MT1 agonist, S 24268, as well as the non-selective antagonist, S 22153. Finally, we also discovered S 25150, the most potent melatonin receptor agonist, so far reported in the literature.

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line
  • Cloning, Molecular / methods*
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Humans
  • Ligands
  • Melatonin / analogs & derivatives*
  • Melatonin / chemistry
  • Melatonin / metabolism*
  • Protein Binding / physiology
  • Receptor, Melatonin, MT1 / agonists
  • Receptor, Melatonin, MT1 / antagonists & inhibitors
  • Receptor, Melatonin, MT1 / genetics
  • Receptor, Melatonin, MT1 / metabolism*
  • Receptor, Melatonin, MT2 / agonists
  • Receptor, Melatonin, MT2 / antagonists & inhibitors
  • Receptor, Melatonin, MT2 / genetics
  • Receptor, Melatonin, MT2 / metabolism*


  • Ligands
  • Receptor, Melatonin, MT1
  • Receptor, Melatonin, MT2
  • Melatonin