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

1. Our aim was to test the hypothesis that selectivity for D-3 dopamin e (DA) receptors may contribute to limbic anti-DA selectivity of S-(+) -aporphine DA partial agonists. 2. Affinity was tested with H-3-emonap ride, 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 we ll as stereoselectivity. Confirmatory or novel D-3/D-2, pharmacologic selectivity was found with several benzamides, thioxanthenes, buspiron e, GBR-12909, and DA agonists including hydroxyaminotetralins [ADTN, ( +)-7-OH-DPAT, (-)-PPHT and its fluorescein derivative], (-)-N-propylno rapomorphine, (-)-3-PPP, (-)-quinpirole, and SDZ-205-502, but neither aminoergoline nor (+)-aporphine partial agonists. 4. The results exten d pharmacologic characterization of D-3-transfected cell membranes but fail to account for the high limbic anti-DA selectivity of S-(+)-apor phines.