Sulpiride isomers exhibit reversed stereospecificity for D-1 and D-2 dopamine receptors in the CNS

We have investigated the stereospecificity of the interaction of (?) and (+)sulpiride with ³H]cis-flupentixol and ³H]spiperone binding to D-1 and D-2 dopamine receptors respectively in rat strialum. Both isomers of sulpiride compete more potently at D-2 vs. D-1 dopamine receptors. (?)Sulpiride is 50-fold more potent than (+)sulpiride in blocking D-2 receptors, while (+)sulpiride is 3-fold more potent than (?)sulpiride at D-1 receptors. This reversed stereospecificity of sulpiride interactions with CNS D-1 and D-2 dopamine receptors is similar to the stereospecificity of sulpiride interactions at DA₁ and DA₂ dopamine receptors in peripheral vascular beds.Biochemical and radioligand binding studies indicate the presence of D-1 and D-2 dopamine receptor subtypes in the central nervous system (CNS) (Creese, Sibley, Hamblin and Leff, 1983). Pharmacological studies suggest that a similar subclassiflcation may be made for dopamine receptors found in peripheral vascular beds based on their postsynaptic (DA₁) or presynaptic (DA₂) localization (for review see Goldberg and Kohli, 1982). Some pharmacological data suggest that similarities may exist between D-1 vs. DA₁ and D-2 vs. DA dopamine receptor subtypes (Goldberg and Kohli, 1982; Creese, 1983; Shepperson, Duval, Massingham and Langer, 1982; Schmidt and Imbs, 1980). Interestingly, all investigations indicate that DA₁ and DA₂ receptors show an opposite stereoselectivity for the (?)(S) and (+)(R) stereoisomers of sulpiride whereby DA₂ receptors are more potently blocked by (?)sulpiride vs. (+)sulpiride and DA₁ receptors are slightly more sensitive to (+)sulpiride vs. (?)sulpiride. The present study reports a similar stereoselectivity for CNS D-2 and D-1 dopamine receptors, respectively, measured by radioligand binding techniques.