{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T23:27:25Z","timestamp":1782257245283,"version":"3.54.5"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology Letters"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1016\/j.toxlet.2022.11.005","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T22:20:09Z","timestamp":1668205209000},"page":"53-61","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Mixture effects of tetrodotoxin (TTX) and drugs targeting voltage-gated sodium channels on spontaneous neuronal activity in vitro"],"prefix":"10.1016","volume":"373","author":[{"given":"Anke M.","family":"Tukker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misha F.","family":"Vrolijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina G.D.M.","family":"van Kleef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick T.H.M.","family":"Sijm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remco H.S.","family":"Westerink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.toxlet.2022.11.005_bib1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/clpt.1984.152","article-title":"Fluoxetine kinetics and protein binding in normal and impaired renal function","volume":"36","author":"Aronoff","year":"1984","journal-title":"Clin. Pharmacol. Ther."},{"issue":"6","key":"10.1016\/j.toxlet.2022.11.005_bib2","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1080\/19336950.2015.1079674","article-title":"Voltage gated sodium channels as drug discovery targets","volume":"9","author":"Bagal","year":"2015","journal-title":"Channels"},{"issue":"2","key":"10.1016\/j.toxlet.2022.11.005_bib3","doi-asserted-by":"crossref","first-page":"693","DOI":"10.3390\/toxins6020693","article-title":"Tetrodotoxin: chemistry, toxicity, source, distribution and detection","volume":"6","author":"Bane","year":"2014","journal-title":"Toxins)"},{"key":"10.1016\/j.toxlet.2022.11.005_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2019.124404","article-title":"Tetrodotoxin in marine bivalves and edible gastropods: a mini-review","volume":"236","author":"Biessy","year":"2019","journal-title":"Chemosphere"},{"issue":"3","key":"10.1016\/j.toxlet.2022.11.005_bib5","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1253\/circj.67.263","article-title":"Ventricular tachyarrhythmias in a canine model of LQT3: arrhythmogenic effects of sympathetic activity and therapeutic effects of mexiletine","volume":"67","author":"Chinushi","year":"2003","journal-title":"Circ. J."},{"issue":"4","key":"10.1016\/j.toxlet.2022.11.005_bib6","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/0002-9149(72)90442-0","article-title":"Plasma levels of lidocaine after intramuscular administration","volume":"29","author":"Cohen","year":"1972","journal-title":"Am. J. Cardiol."},{"issue":"2","key":"10.1016\/j.toxlet.2022.11.005_bib7","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1152\/jn.00093.2016","article-title":"A comparison of computational methods for detecting bursts in neuronal spike trains and their application to human stem cell-derived neuronal networks","volume":"116","author":"Cotterill","year":"2016","journal-title":"J. Neurophysiol."},{"issue":"6 Suppl 4","key":"10.1016\/j.toxlet.2022.11.005_bib8","first-page":"S233","article-title":"The pharmacology and mechanism of action of riluzole","volume":"47","author":"Doble","year":"1996","journal-title":"Neurology"},{"issue":"7","key":"10.1016\/j.toxlet.2022.11.005_bib9","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/sj.mp.4001087","article-title":"Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity","volume":"7","author":"Farber","year":"2002","journal-title":"Mol. Psychiatry"},{"issue":"3","key":"10.1016\/j.toxlet.2022.11.005_bib10","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/cpt1979253345","article-title":"Chloroquine serum concentration and side effects: evidence for dose-dependent kinetics","volume":"25","author":"Frisk-Holmberg","year":"1979","journal-title":"Clin. Pharmacol. Ther."},{"issue":"6","key":"10.1016\/j.toxlet.2022.11.005_bib11","doi-asserted-by":"crossref","DOI":"10.1002\/cpz1.158","article-title":"Culture of rat primary cortical cells for microelectrode array (mea) recordings to screen for acute and developmental neurotoxicity","volume":"1","author":"Gerber","year":"2021","journal-title":"Curr. Protoc."},{"issue":"2","key":"10.1016\/j.toxlet.2022.11.005_bib12","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0896-6273(00)00116-1","article-title":"Nomenclature of voltage-gated sodium channels","volume":"28","author":"Goldin","year":"2000","journal-title":"Neuron"},{"issue":"1","key":"10.1016\/j.toxlet.2022.11.005_bib13","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.brainres.2004.05.076","article-title":"Neuronal network properties of human teratocarcinoma cell line-derived neurons","volume":"1018","author":"Gortz","year":"2004","journal-title":"Brain Res."},{"issue":"1","key":"10.1016\/j.toxlet.2022.11.005_bib14","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/clpt.1991.98","article-title":"Increased carbamazepine plasma concentrations after fluoxetine coadministration","volume":"50","author":"Grimsley","year":"1991","journal-title":"Clin. Pharmacol. Ther."},{"issue":"1\u20132","key":"10.1016\/j.toxlet.2022.11.005_bib15","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0022-510X(01)00613-X","article-title":"Inter- and intraindividual variability of riluzole serum concentrations in patients with ALS","volume":"191","author":"Groeneveld","year":"2001","journal-title":"J. Neurol. Sci."},{"issue":"6","key":"10.1016\/j.toxlet.2022.11.005_bib16","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/clpt.1981.103","article-title":"Kinetics and bioavailability of mexiletine in healthy subjects","volume":"29","author":"Haselbarth","year":"1981","journal-title":"Clin. Pharmacol. Ther."},{"issue":"5","key":"10.1016\/j.toxlet.2022.11.005_bib17","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/j.1600-0404.1982.tb03106.x","article-title":"Clinical and pharmacokinetic observations on sodium valproate - a 5-year follow-up study in 100 children with epilepsy","volume":"65","author":"Henriksen","year":"1982","journal-title":"Acta Neurol. Scand."},{"issue":"2","key":"10.1016\/j.toxlet.2022.11.005_bib18","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/S0031-6997(25)07158-3","article-title":"Tetrodotoxin, saxitoxin and their significance in the study of excitation phenomena","volume":"18","author":"Kao","year":"1966","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.toxlet.2022.11.005_bib19","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.toxlet.2017.02.014","article-title":"Comparison of the acute inhibitory effects of Tetrodotoxin (TTX) in rat and human neuronal networks for risk assessment purposes","volume":"270","author":"Kasteel","year":"2017","journal-title":"Toxicol. Lett."},{"issue":"10","key":"10.1016\/j.toxlet.2022.11.005_bib20","doi-asserted-by":"crossref","first-page":"6384","DOI":"10.3390\/md13106384","article-title":"Tetrodotoxin, an extremely potent marine neurotoxin: distribution, toxicity, origin and therapeutical uses","volume":"13","author":"Lago","year":"2015","journal-title":"Mar. Drugs"},{"issue":"6","key":"10.1016\/j.toxlet.2022.11.005_bib21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.4161\/chan.2.6.7429","article-title":"Interaction between voltage-gated sodium channels and the neurotoxin, tetrodotoxin","volume":"2","author":"Lee","year":"2008","journal-title":"Channels"},{"issue":"4","key":"10.1016\/j.toxlet.2022.11.005_bib22","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1124\/mol.110.064683","article-title":"Molecular model of anticonvulsant drug binding to the voltage-gated sodium channel inner pore","volume":"78","author":"Lipkind","year":"2010","journal-title":"Mol. Pharmacol."},{"issue":"3","key":"10.1016\/j.toxlet.2022.11.005_bib23","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1085\/jgp.20028723","article-title":"Common molecular determinants of flecainide and lidocaine block of heart Na+ channels: evidence from experiments with neutral and quaternary flecainide analogues","volume":"121","author":"Liu","year":"2003","journal-title":"J. Gen. Physiol."},{"issue":"13","key":"10.1016\/j.toxlet.2022.11.005_bib24","doi-asserted-by":"crossref","first-page":"7588","DOI":"10.1073\/pnas.131171798","article-title":"Evolution and divergence of sodium channel genes in vertebrates","volume":"98","author":"Lopreato","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"10","key":"10.1016\/j.toxlet.2022.11.005_bib25","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/nrn1519","article-title":"Interneurons of the neocortical inhibitory system","volume":"5","author":"Markram","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.toxlet.2022.11.005_bib26","unstructured":"J. Melorose, R. Perroy, S. Careas, Tetrodotoxin \u2013 Sigma Aldricth Material Safety Data Sheet. 2005(1), 1\u20135."},{"issue":"1","key":"10.1016\/j.toxlet.2022.11.005_bib27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1085\/jgp.200810103","article-title":"Local anesthetics disrupt energetic coupling between the voltage-sensing segments of a sodium channel","volume":"133","author":"Muroi","year":"2009","journal-title":"J. Gen. Physiol."},{"issue":"2","key":"10.1016\/j.toxlet.2022.11.005_bib28","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0022-3565(25)11961-7","article-title":"Some pharmacological effects of puffer poison","volume":"122","author":"Murtha","year":"1958","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"12","key":"10.1016\/j.toxlet.2022.11.005_bib29","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1002\/mnfr.201400479","article-title":"Detection of marine neurotoxins in food safety testing using a multielectrode array","volume":"58","author":"Nicolas","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"issue":"4","key":"10.1016\/j.toxlet.2022.11.005_bib30","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1124\/mol.114.093104","article-title":"Fluoxetine blocks Nav1.5 channels via a mechanism similar to that of class 1 antiarrhythmics","volume":"86","author":"Poulin","year":"2014","journal-title":"Mol. Pharmacol."},{"issue":"2\u20133","key":"10.1016\/j.toxlet.2022.11.005_bib31","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0920-1211(91)90012-5","article-title":"Pharmacokinetics and safety of lamotrigine (Lamictal) in patients with epilepsy","volume":"10","author":"Ramsay","year":"1991","journal-title":"Epilepsy Res."},{"issue":"14","key":"10.1016\/j.toxlet.2022.11.005_bib32","doi-asserted-by":"crossref","first-page":"5622","DOI":"10.1021\/ac800769e","article-title":"First toxicity report of tetrodotoxin and 5,6,11-trideoxyTTX in the trumpet shell Charonia lampas lampas in Europe","volume":"80","author":"Rodriguez","year":"2008","journal-title":"Anal. Chem."},{"issue":"3","key":"10.1016\/j.toxlet.2022.11.005_bib33","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.mpmed.2015.12.003","article-title":"Quinine and chloroquine","volume":"44","author":"Thanacoody","year":"2016","journal-title":"Medicine"},{"issue":"3","key":"10.1016\/j.toxlet.2022.11.005_bib34","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1365-2125.1986.tb02892.x","article-title":"Flecainide: single and multiple oral dose kinetics, absolute bioavailability and effect of food and antacid in man","volume":"22","author":"Tjandra-Maga","year":"1986","journal-title":"Br. J. Clin. Pharmacol."},{"issue":"3","key":"10.1016\/j.toxlet.2022.11.005_bib35","first-page":"261","article-title":"Is the time right for in vitro neurotoxicity testing using human iPSC-derived neurons?","volume":"33","author":"Tukker","year":"2016","journal-title":"Altex"},{"issue":"1","key":"10.1016\/j.toxlet.2022.11.005_bib36","first-page":"121","article-title":"Towards animal-free neurotoxicity screening: applicability of hiPSC-derived neuronal models for in vitro seizure liability assessment","volume":"37","author":"Tukker","year":"2020","journal-title":"Altex"},{"issue":"12","key":"10.1016\/j.toxlet.2022.11.005_bib37","doi-asserted-by":"crossref","first-page":"7357","DOI":"10.3390\/md13127070","article-title":"Potential threats posed by tetrodotoxins in UK waters: examination of detection methodology used in their control","volume":"13","author":"Turner","year":"2015","journal-title":"Mar. Drugs"},{"issue":"5","key":"10.1016\/j.toxlet.2022.11.005_bib38","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.3390\/toxins7051779","article-title":"First detection of tetrodotoxin in greek shellfish by UPLC-MS\/MS potentially linked to the presence of the dinoflagellate Prorocentrum minimum","volume":"7","author":"Vlamis","year":"2015","journal-title":"Toxins"},{"issue":"10","key":"10.1016\/j.toxlet.2022.11.005_bib39","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.2174\/0929867311320100005","article-title":"Ion channels as drug targets in central nervous system disorders","volume":"20","author":"Waszkielewicz","year":"2013","journal-title":"Curr. Med. Chem."},{"issue":"4","key":"10.1016\/j.toxlet.2022.11.005_bib40","first-page":"371","article-title":"[Toxicity of tetrodotoxin towards mice and rabbits]","volume":"32","author":"Xu","year":"2003","journal-title":"Wei Sheng Yan Jiu"}],"container-title":["Toxicology Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378427422017805?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378427422017805?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T05:28:01Z","timestamp":1759901281000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378427422017805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":40,"alternative-id":["S0378427422017805"],"URL":"https:\/\/doi.org\/10.1016\/j.toxlet.2022.11.005","relation":{},"ISSN":["0378-4274"],"issn-type":[{"value":"0378-4274","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mixture effects of tetrodotoxin (TTX) and drugs targeting voltage-gated sodium channels on spontaneous neuronal activity in vitro","name":"articletitle","label":"Article Title"},{"value":"Toxicology Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxlet.2022.11.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}