A patch clamp study of the effects of ciprofloxacin and biphenyl acetic acid on rat hippocampal neurone GABA(A) and ionotropic 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 mu M) and ciprofloxacin (100 mu M) to 11 +/- 5 and 38 +/- 7% of control, respectively. BPAA (100 mu M) 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 mu M) and ciprofloxacin (0.03 mu M) together with BPAA (100 mu 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 mu M), BPAA (100 mu M), or ciprofloxacin plus BPAA (both at 100 mu M); the responses being greater than or equal to 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.