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It is involved in a variety of physiological and pathological processes, including pacemaking, prolongation of sensory potentials, neuronal injury, chronic pain and diseases such as epilepsy and amyotrophic lateral sclerosis. Despite its importance, neither the molecular basis nor the regulation of I<jats:sub>NaP<\/jats:sub> are sufficiently understood. Of particular significance is a solid knowledge and widely accepted consensus about pharmacological tools for analysing the function of I<jats:sub>NaP<\/jats:sub> and for developing new therapeutic strategies. However, the literature on I<jats:sub>NaP<\/jats:sub> is heterogeneous, with varying definitions and methodologies used across studies. To address these issues, we provide a systematic review of the current state of knowledge on I<jats:sub>NaP<\/jats:sub>, with focus on mechanisms and effects of this current in the central nervous system. We provide an overview of the specificity and efficacy of the most widely used I<jats:sub>NaP<\/jats:sub> blockers: amiodarone, cannabidiol, carbamazepine, cenobamate, eslicarbazepine, ethosuximide, gabapentin, GS967, lacosamide, lamotrigine, lidocaine, NBI-921352, oxcarbazepine, phenytoine, PRAX-562, propofol, ranolazine, riluzole, rufinamide, topiramate, valproaic acid and zonisamide. We conclude that there is strong variance in the pharmacological effects of these drugs, and in the available information. At present, GS967 and riluzole can be regarded <jats:italic>bona fide<\/jats:italic> I<jats:sub>NaP<\/jats:sub> blockers, while phenytoin and lacosamide are blockers that only act on the slowly inactivating component of sodium currents.<\/jats:p>","DOI":"10.1007\/s00424-024-02980-7","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T09:02:07Z","timestamp":1720170127000},"page":"1445-1473","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers"],"prefix":"10.1007","volume":"476","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9630-2553","authenticated-orcid":false,"given":"Peter","family":"M\u00fcller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6243-5582","authenticated-orcid":false,"given":"Andreas","family":"Draguhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4899-8407","authenticated-orcid":false,"given":"Alexei V.","family":"Egorov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"issue":"1","key":"2980_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1085\/jgp.201511492","volume":"147","author":"CA Ahern","year":"2016","unstructured":"Ahern CA, Payandeh J, Bosmans F, Chanda B (2016) The hitchhiker\u2019s guide to the voltage-gated sodium channel galaxy. 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