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Experimental studies showed that centrally active imidazoline compounds belonging to antihypertensive drugs can affect seizure susceptibility. The purpose of this study was to assess the effect of moxonidine, an I<jats:sub>1<\/jats:sub>\u2010imidazoline receptor agonist, on the anticonvulsant efficacy of numerous AEDs (carbamazepine, phenobarbital, valproate, phenytoin, oxcarbazepine, topiramate and lamotrigine) in the mouse model of maximal electroshock. Besides, the combinations of moxonidine and AEDs were investigated for adverse effects in the passive avoidance task and the chimney test. Drugs were administered intraperitoneally (ip). Moxonidine at doses of 1 and 2\u2009mg\/kg ip did not affect the convulsive threshold. Among tested AEDs, moxonidine (2\u2009mg\/kg) potentiated the protective effect of valproate against maximal electroshock. This interaction could be pharmacodynamic because the brain concentration of valproate was not significantly changed by moxonidine. The antihypertensive drug did not cause adverse effects when combined with AEDs. This study shows that moxonidine may have a neutral or positive effect on the anticonvulsant activity of AEDs in patients with epilepsy. The enhancement of the anticonvulsant action of valproate by moxonidine needs further investigations to elucidate potential mechanisms involved.<\/jats:p>","DOI":"10.1111\/bcpt.13669","type":"journal-article","created":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T03:00:51Z","timestamp":1633748451000},"page":"28-34","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Assessment of drug\u2013drug interactions between moxonidine and antiepileptic drugs in the maximal electroshock seizure test in mice"],"prefix":"10.1111","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9610-2532","authenticated-orcid":false,"given":"Krzysztof","family":"\u0141ukawski","sequence":"first","affiliation":[{"name":"Department of Physiopathology Institute of Rural Health  Lublin Poland"},{"name":"Department of Pathophysiology Medical University of Lublin  Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanis\u0142aw Jerzy","family":"Czuczwar","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Medical University of Lublin  Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,10,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00225-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2013.12.032"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-019-03913-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2011.01.003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5922.2011.00269.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.118.016311"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200000004-00005"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152506775268758"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881116652579"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1995.tb02568.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2003.08.001"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13492"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03754-X"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-010-0455-y"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2011.06.030"},{"issue":"2","key":"e_1_2_7_17_1","first-page":"99","article-title":"A simplified method of evaluating dose\u2010effect experiments","volume":"96","author":"Litchfield JT","year":"1949","journal-title":"J Pharmacol Exp Ther"},{"issue":"6","key":"e_1_2_7_18_1","first-page":"782","article-title":"How significant is the difference between drug doses influencing the threshold for electroconvulsions?","volume":"57","author":"\u0141uszczki JJ","year":"2005","journal-title":"Pharmacol Rep"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3458.2003.tb00249.x"},{"issue":"3","key":"e_1_2_7_20_1","first-page":"1001","article-title":"Sodium valproate, but not ethosuximide, produces use\u2010 and voltage\u2010dependent limitation of high frequency repetitive firing of action potentials of mouse central neurons in cell culture","volume":"237","author":"McLean MJ","year":"1986","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(90)90416-7"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(86)90135-6"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200216100-00003"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207450902787165"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702031"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(91)90582-B"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1996.tb00625.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2007.037861"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-008-0046-3"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.2000.tb02164.x"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2009.05.005"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2015.11.001"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.117.243865"}],"container-title":["Basic &amp; 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