Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec QC, Canada.
Fundam Clin Pharmacol. 2012 Oct;26(5):599-608. doi: 10.1111/j.1472-8206.2011.00953.x. Epub 2011 May 30.
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 I(Kr) -, I(Ks) -, and I(Na) -blocking effects of bupropion. Langendorff retroperfusion technique on isolated guinea-pig hearts was used to evaluate the MAPD(90) -, 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 I(Kr) blocker. IC(50) was estimated at 34 μm. In contrast, bupropion had hardly any effect on I(Ks) and I(Na) . Bupropion had no significant MAPD(90) -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 I(Kr) -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.
QRS 增宽和 QT 延长与安非他酮有关。目的是阐明其心脏电生理特性。使用膜片钳技术评估安非他酮对 I(Kr) -、I(Ks) -和 I(Na) -的阻滞作用。使用Langendorff 逆行灌注技术评估安非他酮和两种缝隙连接细胞间通讯抑制剂（甘草次酸和庚醇）对豚鼠心脏 MAPD(90) -、MAP 幅度、相位 0 dV/dt -和 ECG 的调制作用。为了评估它们对心脏细胞间通讯的影响，使用荧光恢复后漂白（FRAP）技术。安非他酮是一种 I(Kr) 阻滞剂。IC(50) 估计为 34 μm。相比之下，安非他酮对 I(Ks) 和 I(Na) 几乎没有影响。安非他酮对 MAPD(90) 没有明显的调制作用。然而，与甘草次酸和庚醇一样，安非他酮导致 MAP 幅度和相位 0 dV/dt 的重要降低。安非他酮还观察到轻微但显著的 QRS 增宽效应。FRAP 实验证实安非他酮抑制缝隙连接细胞间通讯。安非他酮过量时的 QT 延长是由于其 I(Kr) 阻断作用。安非他酮引起的 QRS 增宽与心脏钠通道阻滞无关。安非他酮更像是模拟甘草次酸和庚醇的 QRS 增宽、MAP 幅度和相位 0 dV/dt 降低作用。与 I 类抗心律失常药不同，安非他酮通过减少心脏细胞间耦联引起心脏传导障碍。
