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Hippocampal activity in the presence of quinolones and fenbufen in vitro
W Dimpfel1, M Spüler, A Dalhoff
1Pro Science Private Research Institute, Linden, Federal Republic of Germany.
Abstract:
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. Threshold doses of the quinolones tested (0.25 microM) increased the amplitudes of evoked potentials in the presence of an otherwise ineffective concentration of fenbufen (1 microM) to different degrees, ranging from 39.2% for ciprofloxacin to 72.6% for enoxacin.
Insights
Quinolone antibiotics can cause rare central nervous system side effects. This study found quinolones increase brain excitability, with ciprofloxacin showing the lowest risk, making it a potential drug of choice.
Area of Science:
- Neuropharmacology
- Microbiology
Background:
- Quinolone antibiotics are associated with rare central nervous system (CNS) side effects such as dizziness and convulsions.
- The precise mechanism underlying these CNS effects remains incompletely understood.
Purpose of the Study:
- To investigate the in vitro effects of various quinolones on neuronal excitability in the rat hippocampus.
- To compare the relative neuroexcitatory potential of different quinolone antibiotics.
Main Methods:
- Electrically evoked field potentials in the CA1 region of rat hippocampus slices were used to assess neuronal excitability.
- Dose-dependent effects of nalidixic acid, enoxacin, pefloxacin, norfloxacin, ofloxacin, and ciprofloxacin were evaluated.
- The interaction between quinolones and fenbufen on neuronal activity was also examined.
Main Results:
- All tested quinolones demonstrated a dose-dependent increase in the amplitude of evoked field potentials, indicating enhanced neuronal excitability.
- Enoxacin and nalidixic acid showed the most significant increase in excitability, while ciprofloxacin exhibited the lowest.
- Fenbufen induced spontaneous neuronal firing and potentiated the effects of quinolones on evoked potentials.
Conclusions:
- Quinolones enhance neuronal excitability in a dose-dependent manner.
- Ciprofloxacin appears to be the safest quinolone regarding neuroexcitatory potential.
- Combined use of quinolones with other drugs like fenbufen may increase the risk of CNS side effects.