Introduction: Lamotrigine, an anti-epileptics or a mood-stabilizer for bipolar disorder, has been known to induce hypotension, elevation of the atrial pacing threshold, cardiac conduction delay, Brugada-like electrocardiographic pattern, wide complex tachycardia and cardiac arrest. We studied what types of electrophysiological changes of lamotrigine may reveal these cardiovascular adverse events.
Methods: Lamotrigine was intravenously administered in doses of 0.1, 1 and 10 mg/kg/10 min to halothane-anesthetized dogs (n=4) with monitoring the cardiohemodynamic and electrophysiological variables, possibly providing subtherapeutic to supratherapeutic plasma concentrations.
Results: Although the low or middle dose of lamotrigine did not alter any of the variables, the high dose delayed the intra-atrial, atrioventricular nodal and intra-ventricular conductions with the increase of ventricular refractoriness. 
Conclusion: While lamotrigine by itself may have wide safety margin for hemodynamic variables, its supratherapeutic dose would block Na⁺ channel in the in situ hearts, partly explaining the clinically reported cardiac adverse events. Lamotrigine might unmask Brugada syndrome in patients having genetic risk factors.