Fluoxetine blocks Nav1.5 channels via a mechanism similar to that of class 1 antiarrhythmics.

ABSTRACT: The voltage-gated Nav1.5 channel is essential for the propagation of action potentials in the heart. Malfunctions of this channel are known to cause hereditary diseases. It is a prime target for class 1 antiarrhythmic drugs and a number of antidepressants. Our study investigated the Nav1.5 blocking properties of fluoxetine, a selective serotonin reuptake inhibitor. Nav1.5 channels were expressed in HEK-293 cells, and Na(+) currents were recorded using the patch-clamp technique. Dose-response curves of racemic fluoxetine (IC50 = 39 μM) and its optical isomers had a similar IC50 [40 and 47 μM for the (+) and (-) isomers, respectively]. Norfluoxetine, a fluoxetine metabolite, had a higher affinity than fluoxetine, with an IC50 of 29 μM. Fluoxetine inhibited currents in a frequency-dependent m

SUBMITTER: Poulin H 

PROVIDER: S-EPMC4164981 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature