{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T08:13:35Z","timestamp":1788682415448,"version":"build-2803163510"},"reference-count":110,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRIN","award":["Prot. 2017FJSM9S_005"],"award-info":[{"award-number":["Prot. 2017FJSM9S_005"]}]},{"name":"PRIN","award":["2017\/2018"],"award-info":[{"award-number":["2017\/2018"]}]},{"name":"Fondi Ateneo Uniba","award":["Prot. 2017FJSM9S_005"],"award-info":[{"award-number":["Prot. 2017FJSM9S_005"]}]},{"name":"Fondi Ateneo Uniba","award":["2017\/2018"],"award-info":[{"award-number":["2017\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The voltage-gated sodium channels represent an important target for drug discovery since a large number of physiological processes are regulated by these channels. In several excitability disorders, including epilepsy, cardiac arrhythmias, chronic pain, and non-dystrophic myotonia, blockers of voltage-gated sodium channels are clinically used. Myotonia is a skeletal muscle condition characterized by the over-excitability of the sarcolemma, resulting in delayed relaxation after contraction and muscle stiffness. The therapeutic management of this disorder relies on mexiletine and other sodium channel blockers, which are not selective for the Nav1.4 skeletal muscle sodium channel isoform. Hence, the importance of deepening the knowledge of molecular requirements for developing more potent and use-dependent drugs acting on Nav1.4. Here, we review the available treatment options for non-dystrophic myotonia and the structure\u2013activity relationship studies performed in our laboratory with a focus on new compounds with potential antimyotonic activity.<\/jats:p>","DOI":"10.3390\/ijms24010857","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T04:28:17Z","timestamp":1672806497000},"page":"857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Blockers of Skeletal Muscle Nav1.4 Channels: From Therapy of Myotonic Syndrome to Molecular Determinants of Pharmacological Action and Back"],"prefix":"10.3390","volume":"24","author":[{"given":"Michela","family":"De Bellis","sequence":"first","affiliation":[{"name":"Section of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1078-8490","authenticated-orcid":false,"given":"Brigida","family":"Boccanegra","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro Giovanni","family":"Cerchiara","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-5350","authenticated-orcid":false,"given":"Paola","family":"Imbrici","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-7341","authenticated-orcid":false,"given":"Annamaria","family":"De Luca","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/S2352-4642(19)30425-0","article-title":"Muscle and brain sodium channelopathies: Genetic causes, clinical phenotypes, and management approaches","volume":"4","author":"Matthews","year":"2020","journal-title":"Lancet Child Adolesc. 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