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

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

  • J Med Chem. 2012 Feb 9;55(3):1418-22. doi: 10.1021/jm201197z.
Alessia Catalano 1,  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
Affiliations

Affiliation

  • 1 Dipartimento Farmaco-Chimico, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, 70126 Bari, Italy.
PMID: 22191686 DOI: 10.1021/jm201197z
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.

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