This study investigated the potential convulsive activity of ciprofloxacin in mice and the possible mechanism(s)
of this activity. Intraperitoneal (i.p.) administration of ciprofloxacin into mice resulted in convulsive seizures in
a dose-dependent manner. The clonic median convulsant dose (CD50) of ciprofloxacin in mice was increased
by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine, not changed by pretreatment with
7-nitroindazole and decreased by pretreatment with L-arginine and fenbufen. The increase in nitric oxide (NO)
production andmalondialdehyde (MDA) level as well as the decrease in intracellular reduced glutathione (GSH)
level and glutathione peroxidase (GSH-Px) activity induced by the estimated clonic CD50 of ciprofloxacin in mice
brain was inhibited by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine. These biochemical
alterations were not changed by pretreatment with 7-nitroindazole but enhanced by pretreatment with
L-arginine. The elevation induced by the clonic CD50 of ciprofloxacin in brain glutamate levelwas not changed by
pretreatment with MK-801, alpha-lipoic acid, aminoguanidine or L-arginine. Combined treatment of mice with
fenbufen and ciprofloxacin produced elevation of brain NO production and glutamate andMDA levels as well as
inhibition of brain intracellular GSH level and GSH-Px activity. In addition, i.p. administration of the clonic CD50 of
ciprofloxacin produced an increase in inducible but not in neuronal NO synthasemRNA and protein expressions
in mice brain. These results suggest that elevation of brain glutamate levelswith consequent oxidative stress and
increase in the expression and activity of brain inducible NO synthase may play a pivotal role in ciprofloxacininduced
convulsive seizures.