Literature DB >> 32945812

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

David R Witty1, Giuseppe Alvaro1, Dominique Derjean1, Gerard M P Giblin1, Kevin Gunn1, Charles Large1, David T Macpherson1, Valerie Morisset1, Davina Owen1, Joanne Palmer1, Francois Rugiero1, Simon Tate1, Christopher A Hinckley2, Himanshu Naik2.   

Abstract

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 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.
Copyright © 2020 American Chemical Society.

Entities:  

Year:  2020        PMID： 32945812      PMCID： PMC7488392          DOI： 10.1021/acsmedchemlett.0c00263

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  20 in total

Review 1.  International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels.

Authors:  William A Catterall; Alan L Goldin; Stephen G Waxman
Journal:  Pharmacol Rev       Date:  2005-12       Impact factor: 25.468

2.  Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia: a double-blind, placebo-controlled, randomised withdrawal phase 2a trial.

Authors:  Joanna M Zakrzewska; Joanne Palmer; Valerie Morisset; Gerard Mp Giblin; Mark Obermann; Dominik A Ettlin; Giorgio Cruccu; Lars Bendtsen; Mark Estacion; Dominique Derjean; Stephen G Waxman; Gary Layton; Kevin Gunn; Simon Tate
Journal:  Lancet Neurol       Date:  2017-02-17       Impact factor: 44.182

Review 3.  Sodium channel blockers for neuropathic pain.

Authors:  Valentina Zuliani; Mirko Rivara; Marco Fantini; Gabriele Costantino
Journal:  Expert Opin Ther Pat       Date:  2010-06       Impact factor: 6.674

4.  Synthesis and anticonvulsant activity of a new class of 2-[(arylalky)amino]alkanamide derivatives.

Authors:  P Pevarello; A Bonsignori; P Dostert; F Heidempergher; V Pinciroli; M Colombo; R A McArthur; P Salvati; C Post; R G Fariello; M Varasi
Journal:  J Med Chem       Date:  1998-02-12       Impact factor: 7.446

5.  A novel octahydropyridobenzothiazepine metabolite in human urine: biomimetic formation from the melanogen 5-S-cysteinyldopa and formaldehyde via a peculiar sulfur-controlled double Pictet-Spengler condensation.

Authors:  P Manini; M d'Ischia; G Prota
Journal:  J Org Chem       Date:  2000-07-14       Impact factor: 4.354

6.  Rufinamide attenuates mechanical allodynia in a model of neuropathic pain in the mouse and stabilizes voltage-gated sodium channel inactivated state.

Authors:  Marc R Suter; Guylène Kirschmann; Cedric J Laedermann; Hugues Abriel; Isabelle Decosterd
Journal:  Anesthesiology       Date:  2013-01       Impact factor: 7.892

7.  A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat.

Authors:  Michael F Jarvis; Prisca Honore; Char-Chang Shieh; Mark Chapman; Shailen Joshi; Xu-Feng Zhang; Michael Kort; William Carroll; Brian Marron; Robert Atkinson; James Thomas; Dong Liu; Michael Krambis; Yi Liu; Steve McGaraughty; Katharine Chu; Rosemarie Roeloffs; Chengmin Zhong; Joseph P Mikusa; Gricelda Hernandez; Donna Gauvin; Carrie Wade; Chang Zhu; Madhavi Pai; Marc Scanio; Lei Shi; Irene Drizin; Robert Gregg; Mark Matulenko; Ahmed Hakeem; Michael Gross; Matthew Johnson; Kennan Marsh; P Kay Wagoner; James P Sullivan; Connie R Faltynek; Douglas S Krafte
Journal:  Proc Natl Acad Sci U S A       Date:  2007-05-02       Impact factor: 11.205

8.  Myasthenic syndrome caused by mutation of the SCN4A sodium channel.

Authors:  Akira Tsujino; Chantal Maertens; Kinji Ohno; Xin-Ming Shen; Taku Fukuda; C Michael Harper; Stephen C Cannon; Andrew G Engel
Journal:  Proc Natl Acad Sci U S A       Date:  2003-05-23       Impact factor: 11.205

Review 9.  Cardiac sodium channelopathy associated with SCN5A mutations: electrophysiological, molecular and genetic aspects.

Authors:  Carol Ann Remme
Journal:  J Physiol       Date:  2013-07-01       Impact factor: 5.182

10.  A novel SCN9A mutation responsible for primary erythromelalgia and is resistant to the treatment of sodium channel blockers.

Authors:  Min-Tzu Wu; Po-Yuan Huang; Chen-Tung Yen; Chih-Cheng Chen; Ming-Jen Lee
Journal:  PLoS One       Date:  2013-01-31       Impact factor: 3.240
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  3 in total

1.  BmK DKK13, A Scorpion Toxin, Alleviates Pain Behavior in a Rat Model of Trigeminal Neuralgia by Modulating Voltage-Gated Sodium Channels and MAPKs/CREB Pathway.

Authors:  Ran Yang; Yongbo Song; Haipeng Wang; Chunyun Chen; Fei Bai; Chunli Li
Journal:  Mol Neurobiol       Date:  2022-05-17       Impact factor: 5.590

Review 2.  Inhibition of NaV1.7: the possibility of ideal analgesics.

Authors:  Yutaka Kitano; Tsuyoshi Shinozuka
Journal:  RSC Med Chem       Date:  2022-08-01

3.  Trigeminal neuralgia and genetics: A systematic review.

Authors:  Mari Aaroe Mannerak; Aslan Lashkarivand; Per Kristian Eide
Journal:  Mol Pain       Date:  2021 Jan-Dec       Impact factor: 3.395
  3 in total

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