Safinamide's potential in treating nondystrophic myotonias: Inhibition of skeletal muscle voltage-gated sodium channels and skeletal muscle hyperexcitability in vitro and in vivo.


Journal

Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712

Informations de publication

Date de publication:
06 2020
Historique:
received: 29 10 2019
revised: 14 03 2020
accepted: 19 03 2020
pubmed: 25 3 2020
medline: 31 12 2020
entrez: 25 3 2020
Statut: ppublish

Résumé

The antiarrhythmic sodium-channel blocker mexiletine is used to treat patients with myotonia. However, around 30% of patients do not benefit from mexiletine due to poor tolerability or suboptimal response. Safinamide is an add-on therapy to levodopa for Parkinson's disease. In addition to MAOB inhibition, safinamide inhibits neuronal sodium channels, conferring anticonvulsant activity in models of epilepsy. Here, we investigated the effects of safinamide on skeletal muscle hNa

Identifiants

pubmed: 32205118
pii: S0014-4886(20)30118-7
doi: 10.1016/j.expneurol.2020.113287
pii:
doi:

Substances chimiques

Benzylamines 0
NAV1.4 Voltage-Gated Sodium Channel 0
safinamide 90ENL74SIG
Alanine OF5P57N2ZX

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

113287

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Charlotte Keywood, Elsa Melloni, Gloria Padoani, Silvia Vailati are employees of Zambon S.p.A. and Carla Caccia is a consultant of Zambon S.p.A. The International patent application PCT/EP2019/063733 entitled “Safinamide for treating myotonia” was filed on May 28, 2019 in the name of Zambon S.p.A. Designated inventors are Desaphy J.F., Pierno S., Conte D., Melloni E., Vailati S., Padoani G., and Caccia C.

Auteurs

Jean-François Desaphy (JF)

Department of Biomedical Sciences and Human Oncology, School of Medicine, University of Bari Aldo Moro, Bari, Italy. Electronic address: jeanfrancois.desaphy@uniba.it.

Alessandro Farinato (A)

Department of Pharmacy & Drug Sciences, University of Bari Aldo Moro, Bari, Italy.

Concetta Altamura (C)

Department of Biomedical Sciences and Human Oncology, School of Medicine, University of Bari Aldo Moro, Bari, Italy.

Michela De Bellis (M)

Department of Pharmacy & Drug Sciences, University of Bari Aldo Moro, Bari, Italy.

Paola Imbrici (P)

Department of Pharmacy & Drug Sciences, University of Bari Aldo Moro, Bari, Italy.

Nancy Tarantino (N)

Department of Pharmacy & Drug Sciences, University of Bari Aldo Moro, Bari, Italy.

Carla Caccia (C)

Open R&D Department, Zambon S.p.A., Bresso, MI, Italy.

Elsa Melloni (E)

Open R&D Department, Zambon S.p.A., Bresso, MI, Italy.

Gloria Padoani (G)

Open R&D Department, Zambon S.p.A., Bresso, MI, Italy.

Silvia Vailati (S)

Open R&D Department, Zambon S.p.A., Bresso, MI, Italy.

Charlotte Keywood (C)

Open R&D Department, Zambon S.p.A., Bresso, MI, Italy.

Maria Rosaria Carratù (MR)

Department of Biomedical Sciences and Human Oncology, School of Medicine, University of Bari Aldo Moro, Bari, Italy.

Annamaria De Luca (A)

Department of Pharmacy & Drug Sciences, University of Bari Aldo Moro, Bari, Italy.

Diana Conte (D)

Department of Pharmacy & Drug Sciences, University of Bari Aldo Moro, Bari, Italy.

Sabata Pierno (S)

Department of Pharmacy & Drug Sciences, University of Bari Aldo Moro, Bari, Italy.

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Classifications MeSH