Referenced in: none

Automatically associated channels: Nav1.5

Title: Synthesis and toxicopharmacological evaluation of m-hydroxymexiletine, the first metabolite of mexiletine more potent than the parent compound on voltage-gated sodium channels.

Authors: Alessia Catalano, Jean-François Desaphy, Giovanni Lentini, Alessia Carocci, Antonia Di Mola, Claudio Bruno, Roberta Carbonara, Annalisa De Palma, Roberta Budriesi, Carla Ghelardini, Maria Grazia Perrone, Nicola Antonio Colabufo, Diana Conte Camerino, Carlo Franchini

Journal, date & volume: J. Med. Chem., 2012 Feb 9 , 55, 1418-22

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22191686

Abstract
The first synthesis of m-hydroxymexiletine (MHM) has been accomplished. MHM displayed hNav1.5 sodium channel blocking activity, and tests indicate it to be ∼2-fold more potent than the parent mexiletine and to have more favorable toxicological properties than mexiletine. Thus, MHM and possible related prodrugs might be studied as agents for the treatment of arrhythmias, neuropathic pain, and myotonias in substitution of mexiletine (metabolite switch), which has turned out to be tainted with common toxicity.