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 (FQs) 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 seizures and death. These events were associated with a significant increase in intracerebellar cyclic GMP. 3. Pretreatment with the nitric oxide synthase (NOS) inhibitor, NG-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.
Kohno
K
K
Department of Pharmacology, Gifu University School of Medicine, Japan.
Niwa
M
M
Nozaki
M
M
Uematsu
T
T
Fujimura
H
H
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D002939:Ciprofloxacin / Q000633:toxicity; D003292:Convulsants / Q000633:toxicity; D000242:Cyclic AMP / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015365:Enoxacin / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D015242:Ofloxacin / Q000633:toxicity; D010648:Phenylacetates / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*
D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003292:Convulsants; D004791:Enzyme Inhibitors; D010648:Phenylacetates; D009569:Nitric Oxide; D015365:Enoxacin; C012776:biphenylylacetic acid; D002939:Ciprofloxacin; D016291:Dizocilpine Maleate; D015242:Ofloxacin; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester