Sigma (σ) receptors as potential therapeutic targets to mitigate psychostimulant effects

Adv Pharmacol. 2014;69:323-86. doi: 10.1016/B978-0-12-420118-7.00009-3.

Abstract

Many psychostimulants, including cocaine and methamphetamine, interact with sigma (σ) receptors at physiologically relevant concentrations. The potential therapeutic relevance of this interaction is underscored by the ability to selectively target σ receptors to mitigate many behavioral and physiological effects of psychostimulants in animal and cell-based model systems. This chapter begins with an overview of these enigmatic proteins. Provocative preclinical data showing that σ ligands modulate an array of cocaine and methamphetamine effects are summarized, along with emerging areas of research. Together, the literature suggests targeting of σ receptors as an innovative option for combating undesired actions of psychostimulants through both neuronal and glial mechanisms.

Keywords: Addiction; Cocaine; Glia; Methamphetamine; Neurotoxicity; Sigma receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Central Nervous System Stimulants / metabolism*
  • Clinical Trials as Topic / methods
  • Cocaine / metabolism
  • Drug Delivery Systems / methods*
  • Humans
  • Methamphetamine / metabolism
  • Opipramol / administration & dosage
  • Opipramol / metabolism
  • Protein Binding / physiology
  • Receptors, sigma / agonists
  • Receptors, sigma / antagonists & inhibitors
  • Receptors, sigma / metabolism*
  • Substance-Related Disorders / drug therapy
  • Substance-Related Disorders / metabolism

Substances

  • Central Nervous System Stimulants
  • Receptors, sigma
  • Methamphetamine
  • Opipramol
  • Cocaine