QRS widening and QT prolongation under bupropion: a unique cardiac electrophysiological profile

Abstract
QRS widening and QT prolongation are associated with bupropion. The objectives were to elucidate its cardiac electrophysiological properties. Patch-clamp technique was used to assess the IKr-, IKs-, and INa-blocking effects of bupropion. Langendorff retroperfusion technique on isolated guinea-pig hearts was used to evaluate the MAPD90-, MAP amplitude-, phase 0 dV/dt-, and ECG-modulating effects of bupropion and of two gap junction intercellular communication inhibitors: glycyrrhetinic acid and heptanol. To evaluate their effects on cardiac intercellular communication, fluorescence recovery after photobleaching (FRAP) technique was used. Bupropion is an IKr blocker. IC50 was estimated at 34 mu m. In contrast, bupropion had hardly any effect on IKs and INa. Bupropion had no significant MAPD90-modulating effect. However, as glycyrrhetinic acid and heptanol, bupropion caused important reductions in MAP amplitude and phase 0 dV/dt. A modest but significant QRS-widening effect of bupropion was also observed. FRAP experiments confirmed that bupropion inhibits gap junctional intercellular communication. QT prolongation during bupropion overdosage is due to its IKr-blocking effect. QRS widening with bupropion is not related to cardiac sodium channel block. Bupropion rather mimics the QRS-widening, MAP amplitude- and phase 0 dV/dt -reducing effect of glycyrrhetinic acid and heptanol. Unlike class I anti-arrhythmics, bupropion causes cardiac conduction disturbances by reducing cardiac intercellular coupling.