Background: Cannabinoid receptor 1 has its crystallographic structure available in
complex with agonists and inverse agonists, which paved the way to establish an understanding
of the structural basis of interactions with ligands. Dipyrone is a prodrug with analgesic capabilities
and is widely used in some countries. Recently some evidence of a dipyrone metabolite
acting over the Cannabinoid Receptor 1has been shown.
Objective: Our goal here is to explore the dipyrone metabolite 4-aminoantipyrine as a Cannabinoid
Receptor 1 agonist, reviewing dipyrone characteristics, and investigating the structural
basis for its interaction with the Cannabinoid Receptor 1.
Method: We reviewed here recent functional studies related to the dipyrone metabolite focusing
on its action as a Cannabinoid Receptor 1 agonist. We also analyzed protein-ligand interactions
for this complex obtained through docking simulations against the crystallographic structure
of the Cannabinoid Receptor 1.
Results: Analysis of the crystallographic structure and docking simulations revealed that most
of the interactions present in the docked pose were also present in the crystallographic structure
of Cannabinoid Receptor 1 and agonist.
Conclusion: Analysis of the complex of 4-aminoantipyrine and Cannabinoid Receptor 1 revealed
the pivotal role played by residues Phe 170, Phe 174, Phe 177, Phe 189, Leu 193, Val
196, and Phe 379, besides the conserved hydrogen bond at Ser 383. The mechanistic analysis
and the present computational study suggest that the dipyrone metabolite 4-aminoantipyrine
interacts with the Cannabinoid Receptor 1.