Role of nitric oxide in the convulsive seizures induced by fluoroquinolones coadministered with 4-biphenyl acetic acid

1. Contribution of nitric oxide to the convulsive seizures induced by fluoroquinolones (Fas) coadministered with 4 biphenyl acetic acid (BPAA), the active metabolite of fenbufen, was assessed in mice. 2. Enoxacin+4-biphenyl acetic acid caused clonic seizures in all treated mice, followed by tonic sei zures and death. These events were associated with a significant increase in intracerebellar cyclic GMP. 3. Pretreatment with the nitric oxide synthase (NOS) inhibitor, N-G-nitro-L-arginine methylester (L-NAME), but not with D-NAME, significantly reduced the incidence of convulsions and lethality, as well as the increase in cyclic GMP. 4. Pretreatment with N-methyl-D-aspartic acid (NMDA)-receptor antagonist, MK-801, inhibited only the transition of clonic seizure to tonic seizure without affecting the incidence of clonic seizure and lethality. 5. These findings suggest that FQs+BPAA exert convulsions by activating NOS partly through the mediation of the NMDA receptor in the brain cells. (C) 1997 Elsevier Science Inc.