Amitriptyline May Have Possibility to Induce Brugada Syndrome Rather than Long QT Syndrome

Amitriptyline has been reported to induce long QT syndrome in addition to Brugada syndrome. We qualitatively and quantitatively analyzed the potential of amitriptyline to induce these lethal syndromes by using the halothane-anesthetized dogs (n = 6). Amitriptyline was intravenously administered in doses of 0.1, 1 and 10 mg/kg over 10 min every 20 min, which would provide approximately 1, 10 and 100 times higher plasma concentrations than a therapeutic one, respectively. The low dose hardly altered any of the cardiovascular variables. The middle dose increased the heart rate, cardiac output and left ventricular contractility, but decreased the total peripheral vascular resistance and left ventricular end-diastolic pressure, whereas it did not alter any of the electrocardiographic variables. The high dose decreased the mean blood pressure and left ventricular contractility; suppressed atrioventricular nodal and intraventricular conduction; shortened the repolarization period without altering the J–T _peak c and T _peak–T _end; and prolonged the effective refractory period, providing post-repolarization refractoriness in addition to the enhancement of the middle dose-induced cardiovascular effects. Thus, amitriptyline at up to 100 times its therapeutic concentration may not be associated with the onset of long QT syndrome, but may induce Brugada syndrome.