Pharmacophore Identification for Sigma-1 (σ1) Receptor Binding: Application of the "Deconstruction - Reconstruction - Elaboration" Approach

At least two different types of sigma σ (σ1 and σ2) receptors have been identified. A structural feature common to high-affinity (Ki <10 nM) σ1 ligands is: C-N(R)-X-Ph; both C and Ph are associated with regions of bulk tolerance. Numerous other ligands bind, but typically do so with lower affinity.