Binding of [3H]U-101958 to σ1 receptor-like sites in human cerebellum and neuroblastoma cells

1-Benzyl-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-amino-piperdine ([H-3]U-101958), a dopamine D-4 receptor ligand, was found to bind to a large sigma(1) receptor-like component in human cerebellum and SK-N-MC neuroblastoma cells with high affinity (2-4 nM K-d). By contrast, binding to dopamine D-4 receptors represented 10% or less of the sigma(1) receptor-like site. Considering that U-101958 has been characterized as either a dopamine D-4 receptor agonist or antagonist, depending on the system under study, the observation that U-101958 also binds to sigma(1) receptor-like sires is important for accurate interpretation of the pharmacological actions of this compound. [H-3]U-101958 may be a useful radioligand for sigma(1) rather than dopamine D-4 receptor sites. (C) 1999 Elsevier Science B.V. AU rights reserved.