Background: Cannabinoid Receptor 1 (CB1) is a membrane protein prevalent in
the central nervous system, whose crystallographic structure has recently been solved. Studies
will be needed to investigate CB1 complexes with its ligands and its role in the development
of new drugs.
Objective: Our goal here is to review the studies on CB1, starting with general aspects and
focusing on the recent structural studies, with emphasis on the inverse agonists bound structures.
Methods: We start with a literature review, and then we describe recent studies on CB 1 crystallographic
structure and docking simulations. We use this structural information to depict
protein-ligand interactions. We also describe the molecular docking method to obtain complex
structures of CB 1 with inverse agonists.
Results: Analysis of the crystallographic structure and docking results revealed the residues
responsible for the specificity of the inverse agonists for CB 1. Most of the intermolecular interactions
involve hydrophobic residues, with the participation of the residues Phe 170 and
Leu 359 in all complex structures investigated in the present study. For the complexes with
otenabant and taranabant, we observed intermolecular hydrogen bonds involving residues His
178 (otenabant) and Thr 197 and Ser 383 (taranabant).
Conclusion: Analysis of the structures involving inverse agonists and CB 1 revealed the pivotal
role played by residues Phe 170 and Leu 359 in their interactions and the strong intermolecular
hydrogen bonds highlighting the importance of the exploration of intermolecular interactions
in the development of novel inverse agonists.