Imidazoline binding sites and their ligands: an overview of the different chemical structures

Med Res Rev. 2004 Sep;24(5):639-61. doi: 10.1002/med.20007.


Since Bousquet et al. discovered the imidazoline binding sites (IBS) two decades ago, when they realized that the antihypertensive drug clonidine interacts not only with the alpha2-adrenenoceptors (alpha2-AR) but also with a distinct imidazoline preferring binding site, these receptors have been paid a great deal of attention. At least two subtypes, I1 and I2, have been characterised based on their binding affinity for different radioligands, but their structures still remain unknown. The pharmacological profile of these IBSs has been the objective of several and very thorough reviews. However, a medicinal chemistry overview of the different IBS ligands prepared to date has never been attempted. In this study, we attempt to compile all the different chemical structures reported to date as IBS ligands and classify them in function of their chemical structure and binding affinity for the different IBS subtypes. Thus, we comment on the different endogenous IBS ligands known as well as the drugs described to interact with the I1-IBS which have found application as antihypertensive drugs. Then, we review those compounds described in the literature to interact with the I2-IBS, classifying them by their chemical families (imidazolines, guanidines, 2-aminoimidazolines, beta-carbolines). Finally, some conclusions are drawn.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amidines / chemistry
  • Amidines / metabolism
  • Amidines / pharmacology
  • Animals
  • Antihypertensive Agents / chemistry
  • Antihypertensive Agents / metabolism
  • Antihypertensive Agents / pharmacology
  • Binding Sites
  • Carbolines / chemistry
  • Carbolines / metabolism
  • Carbolines / pharmacology
  • Guanidines / chemistry
  • Guanidines / metabolism
  • Guanidines / pharmacology
  • Humans
  • Imidazoles / chemistry*
  • Imidazoles / metabolism*
  • Imidazoline Receptors
  • Ligands
  • Oxazoles / chemistry
  • Oxazoles / metabolism
  • Receptors, Drug / drug effects
  • Receptors, Drug / metabolism*
  • Rilmenidine
  • Structure-Activity Relationship


  • Amidines
  • Antihypertensive Agents
  • Carbolines
  • Guanidines
  • Imidazoles
  • Imidazoline Receptors
  • Ligands
  • Oxazoles
  • Receptors, Drug
  • 2-imidazoline
  • Rilmenidine