SB269652 is the pioneering drug-like allosteric modulator of the dopamine D2 receptor.

D3 receptor antagonist SB269,652 effectively abolished specific binding of [(3)H]nemanopride and [(3)H]spiperone to Chinese hamster ovary-transfected D(3) receptors when radioligands were used at 0.2 and 0.5 nM, respectively. However, SB269,652 only submaximally inhibited the specific binding of these radioligands when they were employed at 10-fold higher concentrations even at high concentrations (5 μM). By analogy, although SB269,652 potently blocked D(3) receptor-mediated activation of Gα(i3) and phosphorylation of extracellular-signal-regulated kinase (ERK)1/2, when concentrations of dopamine were increased by 10-fold, from 1 μM to 10 μM, SB269,652 only submaximally inhibited dopamine-induced stimulation of Gα(i3) [1].