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 IC(50) value of 6.44 x 10(-4) M, followed by fleroxacin, ofloxacin and levofloxacin, their IC(50) 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 (IC(50)=2.86 x 10(-3) M) and fleroxacin (IC(50)=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).
Zhang
Li-Rong
LR
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 200032, PR China.
Li
Ming-Hua
MH
Cheng
Neng-Neng
NN
Chen
Bin-Yan
BY
Wang
Yong-Ming
YM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D016576:Fleroxacin / Q000494:pharmacology; D024841:Fluoroquinolones / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D064704:Levofloxacin; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D015242:Ofloxacin / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D024841:Fluoroquinolones; D015221:Potassium Channels; D064704:Levofloxacin; D015242:Ofloxacin; D016576:Fleroxacin; C061363:sparfloxacin