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

Article Details

Citation

Copy to clipboard

Catalano A, Desaphy JF, Lentini G, Carocci A, Di Mola A, Bruno C, Carbonara R, De Palma A, Budriesi R, Ghelardini C, Perrone MG, Colabufo NA, Conte Camerino D, Franchini C

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. Epub 2012 Jan 31.

PubMed ID

22191686 [ View in PubMed

]

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 approximately 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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Mexiletine	Sodium channel protein type 5 subunit alpha	IC 50 (nM)	420000	N/A	N/A	Details
Mexiletine	Sodium channel protein type 5 subunit alpha	IC 50 (nM)	58000	N/A	N/A	Details