SCH 23390 blocks D-1 and D-2 dopamine receptors in rat neostriatum in vitro

The agonistic and antagonistic effects of the new compound SCH 23390 were tested in functional model systems for the D-1 dopamine receptor and for the D-2 dopamine receptor in vitro. In superfused rat neostriatal slices the increase in the efflux of cyclic AMP was used as a parameter for D-1 receptor stimulation. D-2 receptor stimulation was measured as the decrease in the K+-evoked release of [3H]-acetylcholine. SCH 23390 had no agonistic activity in these two models. SCH 23390 was a potent antagonist of the stimulating effect of dopamine in the D-1 receptor model (apparent pA2 = 7.28). SCH 23390 also antagonized the effect of the D-2 receptor agonist LY 141865 in the D-2 receptor model (apparent pA2 = 6.34). This D-2 receptor antagonism proved to be of a competitive nature.