Binding of [3H]U-101958 to sigma1 receptor-like sites in human cerebellum and neuroblastoma cells.

1-Benzyl-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-amino-piperidine ([3H]U-101958), a dopamine D4 receptor ligand, was found to bind to a large sigma1 receptor-like component in human cerebellum and SK-N-MC neuroblastoma cells with high affinity (2-4 nM Kd). By contrast, binding to dopamine D4 receptors represented 10% or less of the sigma1 receptor-like site. Considering that U-101958 has been characterized as either a dopamine D4 receptor agonist or antagonist, depending on the system under study, the observation that U-101958 also binds to sigma1 receptor-like sites is important for accurate interpretation of the pharmacological actions of this compound. [3H]U-101958 may be a useful radioligand for sigma1 rather than dopamine D4 receptor sites.