Using sigma-ligands as part of a multi-receptor approach to target diseases of the brain

Expert Opin Ther Targets. 2020 Oct;24(10):1009-1028. doi: 10.1080/14728222.2020.1805435. Epub 2020 Aug 31.

Abstract

Introduction: The sigma receptors are found abundantly in the central nervous system and are targets for the treatment of various diseases, including Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD), depression, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). However, for many of these diseases, other receptors and targets have been the focus of the most, such as acetylcholine esterase inhibitors in Alzheimer's and dopamine replacement in Parkinson's. The currently available drugs for these diseases have limited success resulting in the requirement of an alternative approach to their treatment.

Areas covered: In this review, we discuss the potential role of the sigma receptors and their ligands as part of a multi receptor approach in the treatment of the diseases mentioned above. The literature reviewed was obtained through searches in databases, including PubMed, Web of Science, Google Scholar, and Scopus.

Expert opinion: Given sigma receptor agonists provide neuroprotection along with other benefits such as potentiating the effects of other receptors, further development of multi-receptor targeting ligands, and or the development of multi-drug combinations to target multiple receptors may prove beneficial in the future treatment of degenerative diseases of the CNS, especially when coupled with better diagnostic techniques.

Keywords: Alzheimer’s disease; Parkinson’s disease; multi-targeting drugs; multiple Sclerosis; neurological disease; sigma receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Diseases / drug therapy*
  • Brain Diseases / physiopathology
  • Humans
  • Ligands
  • Molecular Targeted Therapy*
  • Neurodegenerative Diseases / drug therapy
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology
  • Receptors, sigma / agonists*
  • Receptors, sigma / metabolism

Substances

  • Ligands
  • Neuroprotective Agents
  • Receptors, sigma