{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:49:10Z","timestamp":1760147350141,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Varenicline (VAR) is a partial agonist of brain \u03b14\u03b22 nicotinic acetylcholine receptors recommended as a first line pharmacotherapy for smoking cessation. The aim of this study was to examine whether VAR affects the protective activity of four classic antiseizure medications, i.e., carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA) on maximal electroshock (MES)-induced seizures, which may serve as an experimental model of human-generalized tonic-clonic seizures in mice. VAR administered intraperitoneally (i.p.) at a subthreshold dose of 0.5 mg\/kg decreased the protective activity of CBZ against MES-induced convulsions, increasing its median effective dose (ED50) from 10.92 \u00b1 1.0 to 18.15 \u00b1 1.73 mg\/kg (p &lt; 0.01). The effect of VAR was dose-dependent because a lower dose of VAR (0.25 mg\/kg) failed to antagonize the protective activity of CBZ. VAR administered at the subthreshold dose of 0.5 mg\/kg had no impact on the protective activity of PB, PHT, and VPA in the mouse MES model. The inhibitory effect of VAR on the protective activity of CBZ against tonic-clonic convulsions most likely resulted from the pharmacodynamic mechanism(s) and was not associated with the changes in total brain concentrations of CBZ. VAR-evoked alterations in the anticonvulsive activity of CBZ may be of serious concern for epileptic tobacco smokers.<\/jats:p>","DOI":"10.3390\/ijms24032616","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T04:58:25Z","timestamp":1675054705000},"page":"2616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interaction of Varenicline with Classic Antiseizure Medications in the Mouse Maximal Electroshock-Induced Seizure Model"],"prefix":"10.3390","volume":"24","author":[{"given":"Piotr","family":"Bernat","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrycjusz","family":"Ko\u0142odziejczyk","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3059-0393","authenticated-orcid":false,"given":"Jarogniew J.","family":"\u0141uszczki","sequence":"additional","affiliation":[{"name":"Department of Occupational Medicine, Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miros\u0142aw","family":"Zagaja","sequence":"additional","affiliation":[{"name":"Isobolographic Analysis Laboratory, Institute of Rural Health, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Tutka","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"},{"name":"Laboratory for Innovative Research in Pharmacology, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"},{"name":"National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,30]]},"reference":[{"key":"ref_1","first-page":"CD006103","article-title":"Nicotine receptor partial agonists for smoking cessation","volume":"2016","author":"Cahill","year":"2016","journal-title":"Cochrane Database Syst. 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