title: 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 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.
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec QC, Canada.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Caillier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Pilote
authors.forename: Annie
authors.initials: A
authors.lastname: Castonguay
authors.forename: Dany
authors.initials: D
authors.lastname: Patoine
authors.forename: Verlaine
authors.initials: V
authors.lastname: Ménard-Desrosiers
authors.forename: Patrick
authors.initials: P
authors.lastname: Vigneault
authors.forename: Raymond
authors.initials: R
authors.lastname: Hreiche
authors.forename: Jacques
authors.initials: J
authors.lastname: Turgeon
authors.forename: Pascal
authors.initials: P
authors.lastname: Daleau
authors.forename: Yves
authors.initials: Y
authors.lastname: De Koninck
authors.forename: Chantale
authors.initials: C
authors.lastname: Simard
authors.forename: Benoit
authors.initials: B
authors.lastname: Drolet
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D016642:Bupropion / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D016466:CHO Cells; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D062787:Drug Overdose; D004562:Electrocardiography; D055724:Electrophysiological Phenomena; D036681:Fluorescence Recovery After Photobleaching; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006168:Guinea Pigs; D019850:Heptanol / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D051381:Rats
chemical_list: D018687:Antidepressive Agents, Second-Generation; D026902:Potassium Channel Blockers; D016642:Bupropion; D019850:Heptanol; D006034:Glycyrrhetinic Acid