[Melatonin, a pertinent prototype for therapeutic innovation].

Melatonin fulfils most of the requirements of a typical lead compound for rational drug design. We have rationally modified each of its structural features with a view to clarifying their role in drug-receptor interactions (affinity and activity) and to obtain agonist and antagonist ligands which could be used as pharmacological tools and/or as drugs. Molecular modelling studies allow us to propose a pharmacophore model. The naphthalenic bioisostere of melatonin (agomelatin) is currently under clinical (phase II) evaluation and two other compounds have been selected for development.