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-biphenylac etic acid (BPAA) functionally inhibits the gamma-amino-butyric acid (G ABA) receptors and thereby induces clonic convulsions. We examined the effects of ofloxacin and its optical isomers on this quinolone-induce d neurotoxicity. Norfloxacin at 10(-5) M alone or at 10(-7) M in combi nation with BPAA (10(-4) M) inhibited [H-3]muscimol binding to rat bra in synaptic membranes. Ofloxacin and its optical isomers did not affec t 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 slight ly, but significantly, weaker than that of the d-isomer DR-3354 and of loxacin. Intracisternal injection of norfloxacin (5 mu g), ofloxacin, levofloxacin or DR-3354 (50 mu g each) induced clonic convulsions in m ice. The incidence of these convulsions was enhanced by the combinatio n with BPAA (50 mu g). The epileptogenic activity of levofloxacin was also weaker than that of DR-3354 or ofloxacin when quinolones were giv en alone or in combination with BPAA. These results suggest that epile ptogenic activity of quinolones is closely related to the inhibitory p otency in GABA receptor binding and that levoflocxacin may have lower neurotoxicity than ofloxacin and DR-3354.