Homology modelling of the serotoninergic 5-HT2c receptor

J Enzyme Inhib Med Chem. 2006 Jun;21(3):285-92. doi: 10.1080/14756360600700608.

Abstract

Since its discovery, 5-hydroxytryptamine, more usually called serotonin, has been an elusive candidate as a major mood regulator. This capacity gives it a great importance in the treatment of depression. It is within this framework that our work takes place, as it is related more particularly to a new therapeutic class whose leader is agomelatine. This compound binds to the melatoninergic receptors and to the serotoninergic 5-HT2c receptor, giving rise to the MASSA concept (Melatonin Agonist and Selective Serotonin Antagonist). Like the majority of the serotoninergic receptors, the sub-type 5-HT2c is a G-protein coupled receptor (GPCR). The three-dimensional structure of 5-HT2c is not experimentally known, and we thus resorted to comparative homology modelling to build a model allowing us to study its interactions with agomelatine.

MeSH terms

  • Acetamides / chemistry*
  • Acetamides / pharmacology
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cattle
  • Lisuride / chemistry*
  • Lisuride / pharmacology
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Receptor, Serotonin, 5-HT2C / chemistry*
  • Receptor, Serotonin, 5-HT2C / drug effects
  • Receptor, Serotonin, 5-HT2C / genetics
  • Rhodopsin / chemistry*
  • Rhodopsin / drug effects
  • Rhodopsin / genetics
  • Sequence Alignment
  • Structure-Activity Relationship
  • Succinates / chemistry*
  • Succinates / pharmacology

Substances

  • Acetamides
  • Receptor, Serotonin, 5-HT2C
  • Succinates
  • agomelatine
  • sarpogrelate
  • Rhodopsin
  • Lisuride