Characterization of quinolone antibacterial-induced convulsions and increases in nuclear AP-1 DNA- and CRE-binding activities in mouse brain

The quinolone antibacterials enoxacin and norfloxacin (2.5 mg/kg, i.v.) pro voked clonic convulsions in mice treated concomitantly with biphenylacetic acid (BPAA, 100 mg/kg, i.p.), a major metabolite of the nonsteroidal anti-i nflammatory drug fenbufen. Gel-shift assays showed that enoxacin-induced co nvulsions resulted in increases in nuclear activator protein 1 (AP-1) DNA- and cyclic AMP responsive element (CRE)-binding activities in the cerebral cortex and hippocampus, but not in other regions, such as the cerebellum an d thalamus. In contrast, ofloxacin and levofloxacin, at the same doses, in the presence of BPAA did not evoke convulsions or increase these DNA-bindin g activities. Administration of these quinolones and BPAA alone elicited ne ither convulsions nor increases in these DNA-binding activities. These resu lts suggest that the increased nuclear AP-1 DNA- and CRE-binding activities in the cerebral cortex and hippocampus induced by quinolones with BPAA cor related with seizure activities and that these brain regions play pivotal r oles in quinolone-induced convulsions. (C) 1999 Elsevier Science Ltd. All r ights reserved.