Competition between Li + and Na + in sodium transporters and receptors: Which Na + -Binding sites are “therapeutic” Li + targets?

Li + (turquoise), the better charge acceptor, can displace Na + (purple) bound by only one or two aa residues in buried sites. Thus, Li + can displace Na + bound by Asp − and Ser in the A 2A AR/β 1 AR receptor and enhance the metal site's stability, thus prohibiting structural distortions induced by agonist binding, leading to lower cytosolic levels of activated G-proteins, which are hyperactive in bipolar disorder patients.