Allosteric modulators of sigma-1 receptor: A review

Edijs Vavers, Liga Zvejniece, Tangui Maurice, Maija Dambrova

Research output: Contribution to journalReview articlepeer-review

30 Citations (Scopus)


Allosteric modulators of sigma-1 receptor (Sig1R) are described as compounds that can increase the activity of some Sig1R ligands that compete with (+)-pentazocine, one of the classic prototypical ligands that binds to the orthosteric Sig1R binding site. Sig1R is an endoplasmic reticulum membrane protein that, in addition to its promiscuous high-affinity ligand binding, has been shown to have chaperone activity. Different experimental approaches have been used to describe and validate the activity of allosteric modulators of Sig1R. Sig1R-modulatory activity was first found for phenytoin, an anticonvulsant drug that primarily acts by blocking the voltage-gated sodium channels. Accumulating evidence suggests that allosteric Sig1R modulators affect processes involved in the pathophysiology of depression, memory and cognition disorders as well as convulsions. This review will focus on the description of selective and non-selective allosteric modulators of Sig1R, including molecular structure properties and pharmacological activity both in vitro and in vivo, with the aim of providing the latest overview from compound discovery approaches to eventual clinical applications. In this review, the possible mechanisms of action will be discussed, and future challenges in the development of novel compounds will be addressed.

Original languageEnglish
Article number223
JournalFrontiers in Pharmacology
Issue numberMAR
Publication statusPublished - 2019
Externally publishedYes


  • Allosteric modulator
  • E1R
  • Fenfluramine
  • OZP002
  • Phenytoin
  • Sigma-1 receptor (Sig1R)
  • SKF83959
  • SOMCL-668

Field of Science*

  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database


Dive into the research topics of 'Allosteric modulators of sigma-1 receptor: A review'. Together they form a unique fingerprint.

Cite this