Sigma receptors: recent advances and new clinical potentials

Pharm Acta Helv. 2000 Mar;74(2-3):211-8. doi: 10.1016/s0031-6865(99)00034-5.


Several recent advances are leading to a better understanding of sigma receptors. Here we focus on our recent findings regarding cellular functions of sigma-2 receptors and discuss their possible clinical implications. Agonists at sigma-2 receptors induced changes in cell morphology and apoptosis in various cell types. Sigma-2 receptor activation produced both transient and sustained increases in [Ca++]i, derived from different intracellular stores. These changes in [Ca++]i and cytotoxic effects are mediated by intracellular sigma-2 receptors. Sigma-2 agonists induced apoptosis in drug-resistant cancer cells, enhanced the potency of DNA damaging agents, and down-regulated expression of p-glycoprotein mRNA. Thus, sigma-2 receptor agonists may be useful in treatment of drug-resistant cancers. Sigma radioligands have been used in tumor imaging. We also discuss how sigma-2 antagonists might prevent the irreversible motor side effects of typical neuroleptics. Sigma-2 receptors may subserve a novel signalling pathway to apoptosis, involved in regulation of cell proliferation and/or viability.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Receptors, sigma / agonists
  • Receptors, sigma / antagonists & inhibitors
  • Receptors, sigma / classification
  • Receptors, sigma / drug effects*


  • Receptors, sigma
  • sigma-1 receptor
  • sigma-2 receptor