{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:52:06Z","timestamp":1792716726598,"version":"4.5.0"},"reference-count":67,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["K127961"],"award-info":[{"award-number":["K127961"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Sodium channel inhibitors can be used to treat hyperexcitability\u2010related diseases, including epilepsies, pain syndromes, neuromuscular disorders and cardiac arrhythmias. The applicability of these drugs is limited by their nonspecific effect on physiological function. They act mainly by sodium channel block and in addition by modulation of channel kinetics. While channel block inhibits healthy and pathological tissue equally, modulation can preferentially inhibit pathological activity. An ideal drug designed to target the sodium channels of pathological tissue would act predominantly by modulation. Thus far, no such drug has been described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Patch\u2010clamp experiments with ultra\u2010fast solution exchange and photolabeling\u2010coupled electrophysiology were applied to describe the unique mechanism of riluzole on Nav1.4 sodium channels. In silico docking experiments were used to study the molecular details of binding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>We present evidence that riluzole acts predominantly by non\u2010blocking modulation. We propose that, being a relatively small molecule, riluzole is able to stay bound to the binding site, but nonetheless stay off the conduction pathway, by residing in one of the fenestrations. We demonstrate how this mechanism can be recognized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Our results identify riluzole as the prototype of this new class of sodium channel inhibitors. Drugs of this class are expected to selectively prevent hyperexcitability, while having minimal effect on cells firing at a normal rate from a normal resting potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15365","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T19:35:57Z","timestamp":1610739357000},"page":"1200-1217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The mechanism of non\u2010blocking inhibition of sodium channels revealed by conformation\u2010selective photolabeling"],"prefix":"10.1111","volume":"178","author":[{"given":"M\u00e1ty\u00e1s C.","family":"F\u00f6ldi","sequence":"first","affiliation":[{"name":"MTA\u2010ELTE NAP B Opto\u2010Neuropharmacology Group  Budapest Hungary"},{"name":"Plant Protection Institute Centre for Agricultural Research  Martonv\u00e1s\u00e1r Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina","family":"Pesti","sequence":"additional","affiliation":[{"name":"MTA\u2010ELTE NAP B Opto\u2010Neuropharmacology Group  Budapest Hungary"},{"name":"Department of Biochemistry E\u00f6tv\u00f6s Lor\u00e1nd University  Budapest Hungary"},{"name":"School of PhD Studies Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Zboray","sequence":"additional","affiliation":[{"name":"Plant Protection Institute Centre for Agricultural Research  Martonv\u00e1s\u00e1r Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam V.","family":"Toth","sequence":"additional","affiliation":[{"name":"Plant Protection Institute Centre for Agricultural Research  Martonv\u00e1s\u00e1r Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5195-749X","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Heged\u0171s","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Radiation Biology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"M\u00e1ln\u00e1si\u2010Csizmadia","sequence":"additional","affiliation":[{"name":"Motor Pharmacology Research Group, Department of Biochemistry E\u00f6tv\u00f6s Lor\u00e1nd University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lukacs","sequence":"additional","affiliation":[{"name":"MTA\u2010ELTE NAP B Opto\u2010Neuropharmacology Group  Budapest Hungary"},{"name":"Plant Protection Institute Centre for Agricultural Research  Martonv\u00e1s\u00e1r Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9095-8161","authenticated-orcid":false,"given":"Arpad","family":"Mike","sequence":"additional","affiliation":[{"name":"MTA\u2010ELTE NAP B Opto\u2010Neuropharmacology Group  Budapest Hungary"},{"name":"Plant Protection Institute Centre for Agricultural Research  Martonv\u00e1s\u00e1r Hungary"},{"name":"Department of Biochemistry E\u00f6tv\u00f6s Lor\u00e1nd University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.160663"},{"issue":"1","key":"e_1_2_12_3_1","first-page":"S142","article-title":"The concise guide to pharmacology 2019\/20: Ion channels","volume":"176","author":"Alexander S. 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