Details

Autor(en) / Beteiligte

• Witty, David R
• Alvaro, Giuseppe
• Derjean, Dominique
• Giblin, Gerard M. P
• Gunn, Kevin
• Large, Charles
• Macpherson, David T
• Morisset, Valerie
• Owen, Davina
• Palmer, Joanne
• Rugiero, Francois
• Tate, Simon
• Hinckley, Christopher A
• Naik, Himanshu

Titel

Discovery of Vixotrigine: A Novel Use-Dependent Sodium Channel Blocker for the Treatment of Trigeminal Neuralgia

Ist Teil von

• ACS medicinal chemistry letters, 2020-09, Vol.11 (9), p.1678-1687

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Drugs that block voltage-gated sodium channels (NaVs) have utility in treating conditions including pain, epilepsy, and cardiac arrhythmias and as anesthetics ( Lancet Neurol. 2010 9 413 424 ; Expert Opin. Ther. Pat. 2010 20 755 779 ). The identification of compounds with improved efficacy and safety is a key aim for the discovery of improved NaV blocking drugs ( Comprehensive Medicinal Chemistry III; Elsevier, 2017; pp 131−175 ). We report the identification of a novel class of brain penetrant and voltage-gated sodium channel blockers, leading to the discovery of vixotrigine, a use-dependent sodium channel blocker with activity in in vivo models of pain. Vixotrigine has excellent physiocochemical properties for drug development, and both preclinical and clinical data support a safety profile suitable for potential use in neuropathic pain and other conditions. It has shown efficacy in a Phase II study for pain associated with trigeminal neuralgia.