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Renganathan M, Sidach S, Blight AR: Effects of 4-Aminopyridine on Cloned hERG Channels Expressed in Mammalian Cells. Arch Drug Inf. 2009 Sep;2(3):51-57.
INTRODUCTION: Non-clinical evaluation of a medication's potential to induce cardiac toxicity is recommended by regulatory agencies. 4-Aminopyridine (fampridine) is a potassium channel blocker with the demonstrated ability to improve walking ability in patients with multiple sclerosis. We evaluated the in vitro effects of 4-aminopyridine on the human ether-a-go-go-related gene (hERG) channel current, since hERG current inhibition is associated with QT interval prolongation-a precursor to torsade de pointes (TdP). METHODS: 4-Aminopyridine was evaluated in concentrations ranging from 0.1 mM to 30 mM in human embryonic kidney 293 cells stably transfected with the hERG gene; terfenadine 60 nM was used as a positive control. RESULTS AND DISCUSSION: We observed concentration-dependent inhibition of hERG current with 4-aminopyridine doses between 0.3 and 30 mM. The concentration of 3.8 mM resulting in 50% inhibition (IC (50)) is approximately three orders of magnitude higher than expected therapeutic plasma concentrations, suggesting 4-aminopyridine has low potential for prolonging QT interval or inducing TdP. |
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