Ciproxifan, a H3 receptor inverse agonist, reversibly inhibits human monoamine oxidase A and B

Stefanie Hagenow, A. Stasiak, Rona R. Ramsay, Holger Stark

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Ciproxifan is a well-investigated histamine H3 receptor (H3R) inverse agonist/antagonist, showing an exclusively high species-specific affinity at rodent compared to human H3R. It is well studied as reference compound for H3R in rodent models for neurological diseases connected with neurotransmitter dysregulation, e.g. attention deficit hyperactivity disorder or Alzheimer’s disease. In a screening for potential monoamine oxidase A and B inhibition ciproxifan showed efficacy on both enzyme isoforms. Further characterization of ciproxifan revealed IC50 values in a micromolar concentration range for human and rat monoamine oxidases with slight preference for monoamine oxidase B in both species. The inhibition by ciproxifan was reversible for both human isoforms. Regarding inhibitory potency of ciproxifan on rat brain MAO, these findings should be considered, when using high doses in rat models for neurological diseases. As the H3R and monoamine oxidases are all capable of affecting neurotransmitter modulation in brain, we consider dual targeting ligands as interesting approach for treatment of neurological disorders. Since ciproxifan shows only moderate activity at human targets, further investigations in animals are not of primary interest. On the other hand, it may serve as starting point for the development of dual targeting ligands.
Original languageEnglish
Article number40541
Number of pages6
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 13 Jan 2017

Keywords

  • Histamine H3 receptors
  • Monoamine oxidase
  • Inverse agonist/antagonist
  • Dual-target ligand

Fingerprint

Dive into the research topics of 'Ciproxifan, a H3 receptor inverse agonist, reversibly inhibits human monoamine oxidase A and B'. Together they form a unique fingerprint.

Cite this