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QRS widening and QT prolongation under bupropion: a unique cardiac electrophysiological profile
Author(s) -
Caillier Bertrand,
Pilote Sylvie,
Castonguay Annie,
Patoine Dany,
MénardDesrosiers Verlaine,
Vigneault Patrick,
Hreiche Raymond,
Turgeon Jacques,
Daleau Pascal,
De Koninck Yves,
Simard Chantale,
Drolet Benoit
Publication year - 2012
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2011.00953.x
Subject(s) - bupropion , heptanol , pharmacology , qrs complex , medicine , anesthesia , chemistry , cardiology , gap junction , intracellular , biochemistry , smoking cessation , pathology
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 d V /d t ‐, 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 μ m . 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 d V /d t . 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 d V /d t ‐reducing effect of glycyrrhetinic acid and heptanol. Unlike class I anti‐arrhythmics, bupropion causes cardiac conduction disturbances by reducing cardiac intercellular coupling.