Synthesis and Toxicopharmacological Evaluation of m-Hydroxymexiletine, the First Metabolite of Mexiletine More Potent Than the Parent Compound on Voltage-Gated Sodium Channels
详细信息 查看全文
- 作者：Alessia Catalano ; Jean-Fran莽ois 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
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：February 9, 2012
- 年：2012
- 卷：55
- 期：3
- 页码：1418-1422
- 全文大小：240K
- 年卷期：v.55,no.3(February 9, 2012)
- ISSN：1520-4804
文摘
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.