Interaction between substituted 1-[2-(diphenylmethoxy)ethyl] piperazines and dopamine receptors

Substituted 1-2-(diphenylmethoxy)ethyl]piperazines were tested for their affinity to specific ³H]dopamine binding sites in membrane preparations from the corpus striatum of the rat. In particular, 4-(3-phenyl-2-prop(en)yl)- and 4-(3-phenyl-2-butyl)-substitution yielded compounds potent in displacing ³H]dopamine from its binding sites, with IC₅₀-values in the order of 10 nM. There was a significant correlation between the IC₅₀-values determined in this binding assay and the IC₅₀-values obtained for the same compounds in a previous study on their potency to inhibit the uptake of dopamine in synaptosomal preparations of the striatum of the rat. Current insight in structural requirements for binding to dopamine receptors, as obtained mainly with rigid analogues of dopamine, gives no satisfactory explanation for the dopaminergic activity of the piperazine derivatives tested.