title: The TRPM4 channel inhibitor 9-phenanthrol.
abstract: 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.
authors.affiliation: EA 4650, Groupe Signalisation, Electrophysiologie et Imagerie des Lésions d'Ischémie-Reperfusion Myocardique, UCBN, Normandie Université, Caen, France; Department of Applied Science, The College of William and Mary, Williamsburg, VA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Guinamard
authors.forename: T
authors.initials: T
authors.lastname: Hof
authors.forename: C A
authors.initials: CA
authors.lastname: Del Negro
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008564:Membrane Potentials; D049990:Membrane Transport Modulators / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D049990:Membrane Transport Modulators; D010616:Phenanthrenes; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; C091375:9-phenanthrol
keywords: 9-phenanthrol; NSCCa; TRPM4; calcium-activated non-selective cation channel; cardioprotection