title: Melatonin receptors as therapeutic targets in the suprachiasmatic nucleus.
abstract: BACKGROUND
  Disorders of rhythmicity can cause a variety of pathologies and are known to impair processes involved in metabolism, as well as in cardiovascular disease and cancer. Developing strategies to treat or prevent such diseases is a new challenge for medicine. Rhythms depend on a complex multi-oscillatory circadian network which, in mammals, is hierarchically organized with the suprachiasmatic nuclei (SCN) as master clock. The SCN, thus form an ideal structure for target discovery in circadian pathologies.
  
  
  METHODS
  The development of strategies to treat or prevent disorders of rhythmicity is a new challenge for medicine. Several pharmacological approaches have been suggested, but until now, it has been mostly melatonin (MTL) or MTL-agonists which have demonstrated usefulness in modulating clock activities in vivo. A great number of structurally different MTL receptor ligands have been developed, some of which are already approved and marketed as drugs. The MTL receptor involved in phase-shifting circadian rhythms (chronobiotic effect) is the MT1 subtype.
  
  
  CONCLUSIONS
  As the two receptor subtypes for MTL may have divergent functions, the development of highly selective MT1 and MT2 agonists (and antagonists) is key for the discovery of novel therapeutic agents in specifically defined circadian pathologies. The identification of cells expressing the different MTL receptor subtypes should also permit a better understanding of MLT physiology/pharmacology.
authors.affiliation: a Institut des neurosciences cellulaires et Integratives, INCI UPR 3212 , CNRS and the University of Strasbourg , Strasbourg , France.
authors.forename: Paul
authors.initials: P
authors.lastname: Pévet
mesh_terms: D000818:Animals; D021081:Chronobiology Disorders / Q000188:drug therapy* / Q000503:physiopathology; D002940:Circadian Rhythm / Q000502:physiology; D006801:Humans; D008024:Ligands; D008550:Melatonin / Q000008:administration & dosage / Q000819:agonists / Q000378:metabolism; D058990:Molecular Targeted Therapy; D044122:Receptor, Melatonin, MT1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism
chemical_list: D008024:Ligands; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin
keywords: Circadian clock; circadian derived diseases; melatonin; melatonin receptors; suprachiasmatic nuclei