Dopamine receptor occupancy in vivo: behavioral correlates using NNC-112, NNC-687 and NNC-756, new selective dopamine D1 receptor antagonists

The ability of dopamine D2, mixed D1/D2 and selective D1 receptor antagonists, including NNC-112, NNC-687, NNC-756, to inhibit the in vivo binding of [3H]SCH 23390 or [3H]raclopride to dopamine receptors was studied in mice and rats. Furthermore, the dopamine-antagonistic effects of these drugs were also studied in various behavioral models. Significant levels of in vivo receptor blockade were required for antagonism of typical dopamine agonist-mediated behaviors. However, fewer D1 than D2 receptors had to be blocked to produce similar antagonistic effects. Thus, there may be a greater receptor reserve for D2 receptors than for D1 receptors.