{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T06:38:43Z","timestamp":1767163123688,"version":"build-2238731810"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,6,17]],"date-time":"2013-06-17T00:00:00Z","timestamp":1371427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"K\u00f6ln Fortune"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2013,9]]},"abstract":"Summary<\/jats:title>\n \n Purpose<\/jats:title>\n \n Lamotrigine (\n LTG<\/jats:styled-content>\n ) is a popular modern antiepileptic drug (\n AED<\/jats:styled-content>\n ); however, its mechanism of action has yet to be fully understood, as it is known to modulate many members of several ion channel families. In heterologous systems,\n LTG<\/jats:styled-content>\n inhibits Ca\n v<\/jats:sub>\n 2.3 (\n R<\/jats:styled-content>\n \u2010type) calcium currents, which contribute to kainic\u2010acid (\n KA<\/jats:styled-content>\n )\u2013induced epilepsy in vivo. To gain insight into the role of\n R<\/jats:styled-content>\n \u2010type currents in\n LTG<\/jats:styled-content>\n drug action in vivo, we compared the effects of\n LTG<\/jats:styled-content>\n to two other\n AED<\/jats:styled-content>\n s in Ca\n v<\/jats:sub>\n 2.3\u2010deficient mice and controls on\n KA<\/jats:styled-content>\n \u2010induced seizures.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Behavioral seizure rating and quantitative electrocorticography were performed after injection of 20\u00a0mg\/kg (and 30\u00a0mg\/kg)\n KA<\/jats:styled-content>\n . One hour before\n KA<\/jats:styled-content>\n injection, mice were pretreated with 30\u00a0mg\/kg\n LTG<\/jats:styled-content>\n , 50\u00a0mg\/kg topiramate (\n TPM<\/jats:styled-content>\n ), or 30\u00a0mg\/kg lacosamide (\n LSM<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Key Findings<\/jats:title>\n \n Ablation of Ca\n v<\/jats:sub>\n 2.3 reduced total seizure scores by 28.6% (p\u00a0=\u00a00.0012), and pretreatment with\n LTG<\/jats:styled-content>\n reduced seizure activity of control mice by 23.2% (p\u00a0=\u00a00.02). In Ca\n v<\/jats:sub>\n 2.3\u2010deficient mice,\n LTG<\/jats:styled-content>\n pretreatment increased seizure activity by 22.1% (p\u00a0=\u00a00.018) and increased the percentage of degenerated\n CA<\/jats:styled-content>\n 1 pyramidal neurons (p\u00a0=\u00a00.02). All three\n AED<\/jats:styled-content>\n s reduced seizure activity in control mice; however, only the non\u2013calcium channel modulating\n AED<\/jats:styled-content>\n ,\n LSM<\/jats:styled-content>\n , had an anticonvulsive effect in Ca\n v<\/jats:sub>\n 2.3\u2010deficient mice. Furthermore,\n LTG<\/jats:styled-content>\n altered electrocorticographic parameters differently in the two genotypes: decreasing relative power of ictal spikes in control mice but increasing relative power of high frequency fast ripple discharges during seizures in Ca\n v<\/jats:sub>\n 2.3\u2010deficient mice.\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n \n These findings provided the first in vivo evidence for an essential role for Ca\n v<\/jats:sub>\n 2.3 in\n LTG<\/jats:styled-content>\n pharmacology and shed light on a paradoxical effect of\n LTG<\/jats:styled-content>\n in their absence. Furthermore,\n LTG<\/jats:styled-content>\n appears to promote ictal activity in Ca\n v<\/jats:sub>\n 2.3\u2010deficient mice by increasing high frequency components of seizures, resulting in increased neurotoxicity in the\n CA<\/jats:styled-content>\n 1. This paradoxical mechanism, possibly reflecting rebound hyperexcitation of pyramidal\n CA<\/jats:styled-content>\n 1 neurons after increased inhibition, may be key in understanding\n LTG<\/jats:styled-content>\n \u2010induced seizure aggravation observed in clinical practice.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/epi.12250","type":"journal-article","created":{"date-parts":[[2013,6,17]],"date-time":"2013-06-17T09:06:35Z","timestamp":1371459995000},"page":"1542-1550","source":"Crossref","is-referenced-by-count":22,"title":["Retracted<\/i>\n : Ca\n v<\/sub>\n 2.3 (\n R<\/scp>\n \u2010type) calcium channels are critical for mediating anticonvulsive and neuroprotective properties of lamotrigine in vivo"],"prefix":"10.1111","volume":"54","author":[{"given":"Maxine","family":"Dibu\u00e9","sequence":"first","affiliation":[{"name":"Institute for Neurophysiology University of Cologne Cologne Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC) University of Cologne Cologne Germany"},{"name":"Department of Neurosurgery University Hospital Heinrich\u2010Heine\u2010University Duesseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel A.","family":"Kamp","sequence":"additional","affiliation":[{"name":"Institute for Neurophysiology University of Cologne Cologne Germany"},{"name":"Department of Neurosurgery University Hospital Heinrich\u2010Heine\u2010University Duesseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serdar","family":"Alpdogan","sequence":"additional","affiliation":[{"name":"Institute for Neurophysiology University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etienne E.","family":"Tevoufouet","sequence":"additional","affiliation":[{"name":"Institute for Neurophysiology University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfram 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