Rare side effects on the central nervous system including dizziness, restlessness, and even very rare convulsions as reported during the course of antibiotic treatment with quinolones were the topic of a well-controlled in vitro approach. The excitability of brain matter was tested by electrically evoking field potentials in the CA1 region of the rat hippocampus in vitro. Direct effects of nalidixic acid, enoxacin, pefloxacin, norfloxacin, ofloxacin, and ciprofloxacin were found to occur as a dose-dependent increase in amplitude of this field potential, which is in line with the view that the quinolones increase excitability. The highest increase was found with enoxacin and nalidixic acid, and the lowest increase was found with ciprofloxacin. In order to keep the potential risk of the antibiotic therapy as low as possible, ciprofloxacin might be the drug of choice of the quinolones. In contrast to the quinolones, which only increased the amplitudes of electrically evoked potentials, fenbufen induced spontaneous firing in the pyramidal cell layer without stimulation in addition to its dose-dependent effects on the amplitudes of the evoked potentials. (9,11,15,17).However, the concentrations needed for an interaction of quinolones and GABA are rather high and vary among the different quinolones tested by a factor of -100. These differences, recorded in the specific receptor binding and competition in in vitro experiments, do not mirror clinical experience with the various quinolones, as the total incidences of CNS effects are on the average 0.4 to 1.6% (1,5,7,10,16 (3,14). These data indicate, first, that GABA-ergic mechanisms are a necessary but not sufficient prerequisite for effects and, second, that specific ligand receptor studies do not reflect the complex mechanism leading to quinolone-mediated CNS excitation.The aim of the present investigation was to test the ability of different quinolones alone and in combination with fenbufen to influence electrically evoked field potentials in the hippocampal slice preparation. The method of using brain tissue slices as physiologically intact units dates back to 1966 (18). In this ex vivo model, the complex physiology, i.e., the interconnections between neurons as well as between neurons and glial cells is maintained. In the meantime, this technique has been widely used in order to study the physiology of the hippocampus in vitro (for review, see reference 13). The modulatory contribution, especially, of various transmitters to hippocampal excitation and inhibition phenomena could be studied on a cellular level but within the pertinent network (6).(Part of this study has been presented in abstract form at the 3rd International Symposium on New Quinolones, Vancouver, Canada, 1990.) MATERIALS AND METHODS Hippocampal slice preparations were obtained from 15 adult male CD rats (Charles River Wiga). The animals were exsanguinated under slight ether anesthesia, the brain was removed in total, and the hippocampal formation was isolated under microstereoscopic sight. The...
