A patch clamp study of the effects of ciprofloxacin and biphenyl acetic acid on rat hippocampal neurone GABA_A and lonotropic glutamate receptors

The neurotoxic effects of 4-quinolones alone and in combination with certain non-steroidal anti-inflammatory drugs (NSAIDs) may be related to an interaction at GABA_A and/or ionotropic glutamate receptors. In the present study, the effects of the fluoroquinolone, ciprofloxacin, alone and in combination with the NSAID, biphenyl acetic acid (BPAA), were examined on GABA_A-, NMDA-, AMPA-, and kainate-evoked current responses recorded from cultured rat hippocampal neurones, using the whole cell patch clamp technique. GABA-evoked currents were reversibly inhibited by bicuculline (3 μM) and ciprofloxacin (100 μM) to 11 ± 5 and 38 ± 7% of control, respectively. BPAA (100 μM) had little affect on the GABA current (the response was 82 ± 4% of control) but enhanced the inhibitory potency of ciprofloxacin by approx. 3000-fold. The antagonist effects of ciprofloxacin (30 μM) and ciprofloxacin (0.03 μM) together with BPAA (100 μ M) on the GABA-evoked current were not voltage-dependent. Whole cell currents evoked by NMDA, AMPA or kainate were little influenced by ciprofloxacin (100 μM), BPAA (100 μM), or ciprofloxacin plus BPAA (both at 100 μM); the responses being ≥90% of control in all cases. These data suggest that the proconvulsant effects of quinolones when combined with BPAA may be related to antagonism of central GABA_A receptors but not to an interaction at ionotropic glutamate receptors.