The TRPM4 channel inhibitor 9-phenanthrol

Br J Pharmacol. 2014 Apr;171(7):1600-13. doi: 10.1111/bph.12582.


The phenanthrene-derivative 9-phenanthrol is a recently identified inhibitor of the transient receptor potential melastatin (TRPM) 4 channel, a Ca(2+) -activated non-selective cation channel whose mechanism of action remains to be determined. Subsequent studies performed on other ion channels confirm the specificity of the drug for TRPM4. In addition, 9-phenanthrol modulates a variety of physiological processes through TRPM4 current inhibition and thus exerts beneficial effects in several pathological conditions. 9-Phenanthrol modulates smooth muscle contraction in bladder and cerebral arteries, affects spontaneous activity in neurons and in the heart, and reduces lipopolysaccharide-induced cell death. Among promising potential applications, 9-phenanthrol exerts cardioprotective effects against ischaemia-reperfusion injuries and reduces ischaemic stroke injuries. In addition to reviewing the biophysical effects of 9-phenanthrol, here we present information about its appropriate use in physiological studies and possible clinical applications.

Keywords: 9-phenanthrol; NSCCa; TRPM4; calcium-activated non-selective cation channel; cardioprotection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Drug Design
  • Humans
  • Membrane Potentials
  • Membrane Transport Modulators / chemistry
  • Membrane Transport Modulators / pharmacology*
  • Molecular Structure
  • Phenanthrenes / chemistry
  • Phenanthrenes / pharmacology*
  • Signal Transduction / drug effects
  • Structure-Activity Relationship
  • TRPM Cation Channels / antagonists & inhibitors*
  • TRPM Cation Channels / metabolism


  • Membrane Transport Modulators
  • Phenanthrenes
  • TRPM Cation Channels
  • TRPM4 protein, human
  • 9-phenanthrol