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Updated: Aug 7, 2026

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Published on: August 16, 2018

Development of ligands for the peripheral benzodiazepine receptor

Michelle L James1, Silvia Selleri, Michael Kassiou

  • 1Department of Pharmacology, University of Sydney, NSW 2006, Australia.

Current Medicinal Chemistry
|July 18, 2006
PubMed

Insights

Peripheral benzodiazepine receptors (PBR) are key indicators of brain disease activity. Developing selective PBR ligands is crucial for understanding neuroinflammation and developing new diagnostics and therapeutics.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Peripheral benzodiazepine receptor (PBR) is highly expressed in peripheral organs and moderately in the healthy brain.
  • Activated microglial cells are the primary PBR expressers in CNS pathology.
  • PBR over-expression during neuroinflammation indicates its potential as a brain disease activity index.

Purpose of the Study:

  • To review current classes of PBR ligands.
  • To discuss the biological activity and therapeutic potential of PBR ligands.
  • To highlight the need for selective PBR ligands for further research.

Main Methods:

  • Review of existing literature on PBR ligands.
  • Analysis of different classes of PBR ligands including benzodiazepines, isoquinoline carboxamides, indoleacetamides, phenoxyphenyl-acetamides, and pyrazolopyrimidines.
  • Discussion of synthesized analogues for improved affinity and kinetics.

Main Results:

  • Several classes of PBR ligands have been developed, including benzodiazepines, isoquinoline carboxamides, indoleacetamides, phenoxyphenyl-acetamides, and pyrazolopyrimidines.
  • Conformationally restrained analogues show promise for enhanced affinity and brain kinetics.
  • PBR is implicated in cell proliferation, apoptosis, steroidogenesis, porphyrin transport, and immunomodulation, though its precise physiological role remains unclear.

Conclusions:

  • PBR is a significant target for therapeutic and diagnostic development in CNS pathology.
  • Selective PBR ligands are essential for elucidating PBR's physiological role and underlying pathological pathways.
  • Further research with novel PBR ligands may reveal PBR subtypes and precise localization.

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