en Pharmacology Pharmacology Original Research Original Research <strong>Background: </strong>Lamotrigine (LTG) is an antiepileptic drug used in the treatment of seizures, mood disorders, and cognitive problems. The cardiac effects of LTG, such as LTG toxicity and SUEDP, have been studied. This is an in vitro study examining the effect of LTG on isolated atria of guinea pigs.<br> &nbsp;&nbsp; <strong>Methods:</strong> The atria of 21 male Guinea pigs were isolated and stabilized in Krebs-solution and physiologic condition. The rhythm of contraction, contractile force, and heart rate were recorded. In 7 atria, LTG at the doses of 2, 4, 8, and 16 mg/mL were added and the contractile forces and heart rates were recorded and compared together. In the next step, in 14 atria, 8 were pretreated with LTG, and 6 without pretreatment were exposed to ouabain, and the times of the onset of effect, arrhythmia, and asystole were recorded. The statistical comparisons were made by using Student&rsquo;s t test and repeated measure analysis of variance followed by the Bonferroni method.<br> <strong>&nbsp;&nbsp; Results: </strong>Lamotrigine (4, 8, and 16 mg/mL) significantly decreased the heart rate and contractile force of the isolated guinea pigs&rsquo; atria (P < .001). Pretreatment with LTG significantly increased the mean time of onset of the effect of ouabain, the onset of ouabain-induced arrhythmia, and time of ouabain-induced asystole (P < .001).<br> &nbsp;&nbsp; <strong>Conclusion:</strong> LTG reduces the heart rate and contractile force, and also inhibit ouabain induced-arrhythmia of the isolated atria of guinea pigs.<br> &nbsp; Lamotrigine, Arrhythmia, Sudden Unexpected Death in Epilepsy, Cardiac Effect, Cardiac Arrest 1032 1036 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-178-6&slc_lang=en&sid=1 Marjan Mirsalehi mmirsalehi@gmail.com 200319475328460068788 200319475328460068788 Yes ENT and Head & Neck Research Center and Department, Hazrat Rasoul Hospital, The Five Senses Health institute, Iran University of Medical Sciences, Tehran, Iran Golrokh Malihi malihi1@yahoo.com 200319475328460068789 200319475328460068789 No Fargol Research Group, Ballwin, Missouri, USA Eshagh Bahrami bahrami_eses@yahoo.com 200319475328460068790 200319475328460068790 No Department of Neurosurgery, Hazrat Rasoul Hospital, Iran University of Medical Sciences, Tehran, Iran Zeinab Akbarnejad Zeinabakbarnejad8@gmail.com 200319475328460068791 200319475328460068791 No ENT and Head & Neck Research Center and Department, Hazrat Rasoul Hospital, The Five Senses Health institute, Iran University of Medical Sciences, Tehran, Iran Sayedali Ahmadi ahmadi.as@iums.ac.ir 200319475328460068792 200319475328460068792 No Department of Neurosurgery, Hazrat Rasoul Hospital, Iran University of Medical Sciences, Tehran, Iran