QRS widening and QT prolongation under bupropion: a unique cardiac electrophysiological profile
- 30 May 2011
- journal article
- research article
- Published by Wiley in Fundamental & Clinical Pharmacology
- Vol. 26 (5), 599-608
- https://doi.org/10.1111/j.1472-8206.2011.00953.x
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.Keywords
This publication has 29 references indexed in Scilit:
- Bupropion-Associated QRS Prolongation Unresponsive to Sodium Bicarbonate TherapyClinical Journal of Sport Medicine, 2009
- Biophysical characterization of a new SCN5A mutation S1333Y in a SIDS infant linked to long QT syndromeFEBS Letters, 2009
- Response to “Use of Lipid Emulsion in the Resuscitation of a Patient With Prolonged Cardiovascular Collapse After Overdose of Bupropion and Lamotrigine”Annals of Emergency Medicine, 2008
- Cardiotoxicity Associated With Accidental Bupropion Ingestion in a ChildPediatric Emergency Care, 2007
- Cardiogenic shock and status epilepticus after massive bupropion overdoseClinical Toxicology, 2007
- Gap junctional intercellular communication capacity by gap‐FRAP technique: A comparative studyBiotechnology Journal, 2007
- Intentional bupropion overdosesThe Journal of Emergency Medicine, 2004
- Reversible Inhibition of Gap Junctional Intercellular Communication, Synchronous Contraction, and Synchronism of Intracellular Ca2+ Fluctuation in Cultured Neonatal Rat Cardiac Myocytes by HeptanolExperimental Cell Research, 1995
- Bupropion overdose and seizureThe American Journal of Emergency Medicine, 1994
- Electrophysiological Effects of Antidepressants on Mammalian Hearts and Crayfish Giant AxonJournal of Cardiovascular Pharmacology, 1981