Mechanisms of QT prolongation by buprenorphine cannot be explained by direct hERG channel block

Tran PN, Sheng J, Randolph AL, Baron CA, Thiebaud N, Ren M, Wu M, Johannesen L, Volpe DA, Patel D, Blinova K, Strauss DG and Wu WW.

PLOS One, 2020



Buprenorphine is used to manage pain and addiction but has been shown to cross the QTc prolongation of regulatory concern.  Electrophysiological studies of the effect of the drug were investigated due to the long QT prolongation being associated with Torsades de Pointes, a rare but potentially fatal arrhythmia.  The authors characterized the effect of buprenorphine on cardiac hERG ion channels and cardiac action potentials.  Multielectrode array (MEA) recordings were made on iPSC-derived CMs.  The experiments showed a lack of effected on delayed repolarization at clinically relevant concentrations and therefore no evidence that buprenorphine is associated with TdP.