Structural features important for sigma 1 receptor binding

J Med Chem. 1994 Apr 15;37(8):1214-9. doi: 10.1021/jm00034a020.


Two problems that have hampered sigma receptor research are (i) a lack of high-affinity agents and (ii) the recent identification of multiple populations of sigma receptors (i.e., sigma 1 and sigma 2 sites). Recently, several high-affinity sigma ligands have been identified, and the term superpotent sigma ligands has been coined to describe agents with Ki values of < 1 nM. We have previously shown that appropriately N-substituted phenylalkylamines bind at sigma receptors with high affinity. In the present investigation, we examine the structure-affinity relationships of these phenylalkylamine derivatives for sigma 1 binding and describe some of the first superpotent sigma 1 ligands. A binding model was developed to account for the structural features of the phenylalkylamines that appear to be important for the interaction of these agents with sigma 1 sites.

Publication types

  • Comparative Study

MeSH terms

  • Alkylation
  • Amines / chemical synthesis*
  • Amines / chemistry
  • Amines / metabolism
  • Animals
  • Binding Sites
  • Brain / metabolism
  • Cell Membrane / metabolism
  • Cyclization
  • Guinea Pigs
  • Methylation
  • Molecular Structure
  • Receptors, sigma / chemistry
  • Receptors, sigma / metabolism*
  • Stereoisomerism
  • Structure-Activity Relationship


  • Amines
  • Receptors, sigma