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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Disease Models, Animal*
-
Female
-
Humans
-
Imidazoles / chemistry
-
Imidazoles / therapeutic use*
-
Lymph Nodes / drug effects
-
Lymph Nodes / metabolism
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Transgenic
-
Multiple Sclerosis / complications
-
Multiple Sclerosis / drug therapy*
-
Multiple Sclerosis / metabolism
-
Neuroprotective Agents / therapeutic use*
-
Optic Neuritis / drug therapy*
-
Optic Neuritis / etiology
-
Optic Neuritis / metabolism
-
Retinal Ganglion Cells / drug effects*
-
Voltage-Gated Sodium Channels / metabolism*
Substances
-
Imidazoles
-
Neuroprotective Agents
-
Voltage-Gated Sodium Channels