title: Inhibition by fluoroquinolones of K(+) currents in rat dissociated hippocampal neurons.
abstract: 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).
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 200032, PR China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Zhang
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Li
authors.forename: Neng-Neng
authors.initials: NN
authors.lastname: Cheng
authors.forename: Bin-Yan
authors.initials: BY
authors.lastname: Chen
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Wang
mesh_terms: 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
chemical_list: D024841:Fluoroquinolones; D015221:Potassium Channels; D064704:Levofloxacin; D015242:Ofloxacin; D016576:Fleroxacin; C061363:sparfloxacin