Sodium Channel Blockers for the Treatment of Pain

Witty, David R.; MacPherson, David T.; Giblin, Gerard M.P.

doi:10.1016/b978-0-12-409547-2.12439-4

Cited by 3 publications

(1 citation statement)

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“…The mechanism of action of several drugs in current clinical practice is, at least in part, due to nonselective blockade of voltage-gated sodium channels. − For example, lamotrigine for epilepsy and bipolar disorder and carbamazepine for epilepsy and trigeminal neuralgia are characterized as nonselective sodium channel blockers. However, the utility of these drugs is limited by side effects and multiple drug–drug interactions that require careful and prolonged titration to the effective clinical dose.…”

Section: Introductionmentioning

confidence: 99%

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

Witty

Alvaro

Derjean

et al. 2020

ACS Med. Chem. Lett.

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Drugs that block voltage-gated sodium channels (NaVs) have utility in treating conditions including pain, epilepsy, and cardiac arrhythmias and as anesthetics (Lancet Neurol.20109413424; Expert Opin. Ther. Pat.201020755779). The identification of compounds with improved efficacy and safety is a key aim for the discovery of improved NaV blocking drugs (Comprehensive Medicinal Chemistry IIIElsevier2017131175). 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.

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Section: Introductionmentioning

confidence: 99%