Imidazol-1-ylethylindazole Voltage-Gated Sodium Channel Ligands Are Neuroprotective during Optic Neuritis in a Mouse Model of Multiple Sclerosis
- Resource Type
- Authors
- Browne, Lorcan; Lidster, Katie; Al-Izki, Sarah; Clutterbuck, Lisa; Posada, Cristina; Chan, A. W. Edith; Riddall, Dieter; Garthwaite, John; Baker, David; Selwood, David L.
- Source
- Journal of Medicinal Chemistry
- Subject
- Article
- Language
- English
- ISSN
- 1520-4804
0022-2623
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.