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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Determination of the excitatory potencies of fluoroquinolones in the central nervous system by an in vitro model.

Fluoroquinolones have been reported to induce central nervous system side effects, including seizures and psychiatric events. Although relatively rare in patients up to now, the proconvulsant activity depends on the chemical structure and might be a critical endpoint of some new representatives of this valuable class of antimicrobials. The electrophysiological determination of field potentials in the CA1 region of the rat hippocampus slice allowed an assessment of the excitatory potential of fluoroquinolones and might be predictive for their neurotoxic potency in vivo. An optimization of this method and its extension to other fluoroquinolones resulted in a defined rank order. Well-known already-marketed quinolones as well as some fluoroquinolones under evaluation and development were used. The dose range tested was between 0.5 and 4 mumol/liter, which was comparable to the therapeutic concentration in the brain. All tested compounds increased the population spike amplitude in a concentration-dependent manner, and the resulting excitatory potency was highly dependent on the chemical structure, with compounds ranging from least to most excitatory as follows: ofloxacin, ciprofloxacin, nalidixic acid, moxifloxacin, BAY x 8843, [corrected] fleroxacin, lomefloxacin, enoxacin, clinafloxacin (much more excitatory than enoxacin), tosufloxacin, trovafloxacin, BAY 15-7828, and BAY x 9181 (much more excitatory than BAY 15-7828). The proposed hippocampus slice model not only is suitable for giving valuable alerts as to convulsive potential during candidate selection but also enables mechanistic investigations. These investigations pointed to the N-methyl-D-aspartate receptor as the probable target of the fluoroquinolone effects.[1]


  1. Determination of the excitatory potencies of fluoroquinolones in the central nervous system by an in vitro model. Schmuck, G., Schürmann, A., Schlüter, G. Antimicrob. Agents Chemother. (1998) [Pubmed]
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