Hypothetical binding mode of SB269652 to dopamine receptor dimer and monomer. SB269652 is composed of three chemical parts, the 7CN-THIQ group, the trans-cyclohexylene spacer in the middle, and the indole-2-carboxamide tail. On the left, SB269652 binds in a bitopic mode to one protomer of the dopamine dimer, the 7CN-THIQ group to the orthosteric site and the indole-2-carboxamide group to the allosteric site (Allo1), to influence dopamine binding on the second protomer (black arrows) through an effect across the dimer (white arrow). On the right, SB269652 binds to the dopamine-occupied receptor and prevents agonist dissociation from the monomer (crossed black arrow). In this last configuration, the 7CN-THIQ group could engage an additional allosteric binding site (Allo2). Diagram was modified from Rossi et al. (2017) [14].