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

Abstract

1. 1. Contribution of nitric oxide to the convulsive seizures induced by fluoroquinolones (FQs) coadministered with 4-biphenyl acetic acid (BPAA), the active metabolite of fenbufen, was assessed in mice. 2. 2. Enoxacin+4-biphenyl acetic acid caused clonic seizures in all treated mice, followed by tonic seizures and death. These events were associated with a significant increase in intracerebellar cyclic GMP. 3. 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. 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. 5. These findings suggest that FQs+BPAA exert convulsions by activating NOS partly through the mediation of the NMDA receptor in the brain cells.