Inhibition by fluoroquinolones of K+ currents in rat dissociated hippocampal neurons

The effects of four fluoroquinolones (sparfloxacin, fleroxacin, ofloxacin and levofloxacin) on K+ currents were investigated in pyramidal neurons acutely isolated from rat hippocampus, to evaluate their relative, potencies for inhibiting these channels. Using patch-clamp electrophysiological techniques, we found that all four compounds inhibited the delayed rectifier K+ current (I-K), but with different potencies. Sparfloxacin was the most potent compound, displaying an IC50 value of 6.44 x 10(-4) M, followed by fleroxacin, ofloxacin and levofloxacin, their IC50 values being 7.09 X 10(-3), 8.42 x 10(-3) and 1.10 x 10(-2) M, respectively. In contrast, the fast transient K+ current (I-A) was blocked only by sparfloxacin (IC50 = 2.86 x 10(-3) M) and fleroxacin (IC50=4.38 x 10(-3) M), but not by ofloxacin and levofloxacin even at concentrations up to 1 mM. The K+ current inhibition was reversible after washout of the compounds. Further study is needed to clarify the possible involvement of this novel action in the adverse effects of fluoroquinolones in the central nervous system (CNS). (C) 2003 Elsevier Science B.V. All rights reserved.