N-(1-arylpropionyl)-4-aryltetrahydropyridines, a new class of high-affinity selective sigma receptor ligands.

A series of N-(1-arylpropionyl)-4-aryl-1,2,3,6-tetrahydropyridines, prepared by simple Mannich condensations, have been found by radioligand binding assays to have moderate to high affinity (IC 50 0.5-500 nM) for bovine cerebellar a receptor/binding sites and no measurable affinity (IC 50 >5000 nM) for bovine striatal D 2 receptors. The most active of these compounds rival in potency the most active a ligands previously reported. Three of these a-active compounds were screened for pharmacological activity under the NIMH-NovaScreen program and showed moderate affinity only for D 2 and 5-HT 2 receptors among the 40 sites assayed