Beyond purinergic signaling: Dual ligand approaches to multitarget drug discovery

Purinergic receptors represent an attractive target for treating numerous multifactorial diseases currently considered incurable. Multitargeted agents binding purinergic receptors show considerable promise in preclinical studies in several diseases. Most of the multifactorial pathologies for which no therapy is currently known represent the greatest challenge for the pharmaceutical community. Molecules directed simultaneously toward multiple targets could counteract the redundancy phenomena typical of biological systems and avoid the side effects associated with drug cocktails. This review is intended to provide a summary of the most significant dual ligands able to interact with purinergic receptors and other G-protein-coupled receptors or enzymes.