N-Arylalkylpiperidines as High-Affinity Sigma-1 and Sigma-2 Receptor Ligands: Phenylpropylamines as Potential Leads for Selective Sigma-2 Agents

To delineate the differences between the structural requirements necessary for recognition at sigma-1 and sigma-2 receptors, a range of phenethyl- and phenylpropylpiperidines were evaluated in binding assays. Phenethylpiperidines were found to favor sigma-1 receptors, whereas phenylpropylpiperidines tend to favor sigma-2 receptors. It appears that phenylpropylamine is a potential pharmacophore for selective sigma-2 ligands.