Levofloxacin, an optical isomer of ofloxacin, has attenuated epileptogenic activity in mice and inhibitory potency in GABA receptor binding.

The combination of some new quinolone antibacterials with 4-biphenylacetic acid (BPAA) functionally inhibits the gamma-amino-butyric acid (GABA) receptors and thereby induces clonic convulsions. We examined the effects of ofloxacin and its optical isomers on this quinolone-induced neurotoxicity. Norfloxacin at 10(-5) M alone or at 10(-7) M in combination with BPAA (10(-4) M) inhibited [3H]muscimol binding to rat brain synaptic membranes. Ofloxacin and its optical isomers did not affect muscimol binding by themselves. While they slightly reduced muscimol binding at 10(-4) M in combination with BPAA, the inhibitory activity of the l-isomer levofloxacin (DR-3355) on muscimol binding was slightly, but significantly, weaker than that of the d-isomer DR-3354 and ofloxacin. Intracisternal injection of norfloxacin (5 micrograms), ofloxacin, levofloxacin or DR-3354 (50 micrograms each) induced clonic convulsions in mice. The incidence of these convulsions was enhanced by the combination with BPAA (50 micrograms). The epileptogenic activity of levofloxacin was also weaker than that of DR-3354 or ofloxacin when quinolones were given alone or in combination with BPAA. These results suggest that epileptogenic activity of quinolones is closely related to the inhibitory potency in GABA receptor binding and that levofloxacin may have lower neurotoxicity than ofloxacin and DR-3354.