title: Imidazol-1-ylethylindazole voltage-gated sodium channel ligands are neuroprotective during optic neuritis in a mouse model of multiple sclerosis.
abstract: A series of imidazol-1-ylethylindazole sodium channel ligands were developed and optimized for sodium channel inhibition and in vitro neuroprotective activity. The molecules exhibited displacement of a radiolabeled sodium channel ligand and selectivity for blockade of the inactivated state of cloned neuronal Nav channels. Metabolically stable analogue 6 was able to protect retinal ganglion cells during optic neuritis in a mouse model of multiple sclerosis.
authors.affiliation: Biological and Medicinal Chemistry, Wolfson Institute for Biomedical Science, University College London , Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Lorcan
authors.initials: L
authors.lastname: Browne
authors.forename: Katie
authors.initials: K
authors.lastname: Lidster
authors.forename: Sarah
authors.initials: S
authors.lastname: Al-Izki
authors.forename: Lisa
authors.initials: L
authors.lastname: Clutterbuck
authors.forename: Cristina
authors.initials: C
authors.lastname: Posada
authors.forename: A W Edith
authors.initials: AW
authors.lastname: Chan
authors.forename: Dieter
authors.initials: D
authors.lastname: Riddall
authors.forename: John
authors.initials: J
authors.lastname: Garthwaite
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.forename: David L
authors.initials: DL
authors.lastname: Selwood
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009902:Optic Neuritis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D018696:Neuroprotective Agents; D061566:Voltage-Gated Sodium Channels