S33084, a novel, potent, selective, and competitive antagonist at dopamine D(3)-receptors : II. Functional and behavioral profile compared with GR218,231 and L741,626

The benzopyranopyrrole S33084 displayed pronounced affinity (pKi 5 9.6) for cloned human hD3-receptors, and.100-fold lower affinity for hD2 and all other receptors (.30) examined. S33084 concentration dependently, potently, and competitively (pA2 5 9.7) antagonized dopamine (DA)-induced [ 35S]guanosine-59- O-(3-thio)triphosphate (GTPgS) binding at hD3-receptors. It also concentration dependently abolished stimulation by DA of hD3-receptor-coupled mitogen-activated protein kinase. Ad-ministered alone, S33084 did not modify dialysate levels of DA in the frontal cortex, nucleus accumbens, or striatum of freely moving rats, nor the firing rate of ventrotegmental dopaminer-gic cell bodies. Furthermore, it had minimal effect on DA turn-over in mesocortical, mesolimbic, and nigrostriatal projectio