S-(+)-APORPHINES ARE NOT SELECTIVE FOR HUMAN D-3 DOPAMINE-RECEPTORS

1. Our aim was to test the hypothesis that selectivity for D-3 dopamine (DA) receptors may contribute to limbic anti-DA selectivity of S-(+)-aporphine DA partial agonists. 2. Affinity was tested with H-3-emonapride, using human D-3 receptors in mouse fibroblasts and D-2 receptors in rat striatal tissue. 3. D-3 receptors showed a picomolar affinity for H-3-emonapride, Na+ dependence, and reversible saturability, as well as stereoselectivity. Confirmatory or novel D-3/D-2, pharmacologic selectivity was found with several benzamides, thioxanthenes, buspirone, GBR-12909, and DA agonists including hydroxyaminotetralins [ADTN, (+)-7-OH-DPAT, (-)-PPHT and its fluorescein derivative], (-)-N-propylnorapomorphine, (-)-3-PPP, (-)-quinpirole, and SDZ-205-502, but neither aminoergoline nor (+)-aporphine partial agonists. 4. The results extend pharmacologic characterization of D-3-transfected cell membranes but fail to account for the high limbic anti-DA selectivity of S-(+)-aporphines.