This study evaluated the effectiveness of
fosphenytoin as a single or adjunctive
anticonvulsant treatment for
nerve agent-induced
status epilepticus. Guinea pigs, implanted with cortical electroencephalographic (EEG) recording
electrodes, were pretreated with
pyridostigmine bromide (0.026 mg/kg, intramuscular (i.m.)) 30 min before challenge with 56 micrograms/kg, subcutaneous (s.c.), (2 x LD50) of the
nerve agent soman. One min after
soman, the animals were treated (i.m.) with 2 mg/kg
atropine sulfate admixed with 25 mg/kg of the
oxime 2-pralidoxime
chloride, and the EEG was observed for seizure onset. When administered (intraperitoneal, i.p.) therapeutically 5 min after seizure onset, only the highest
fosphenytoin dose (180 mg/kg) was capable of terminating seizure activity in 50% of the animals tested (3 of 6). When
fosphenytoin (18-180 mg/kg) was administered as a pretreatment, i.
p., 30 min before
soman challenge,
seizures were blocked or terminated in a dose-dependent fashion (ED50 = 61.8 mg/kg; 40.5-94.7 mg/kg = 95% confidence limits). Combinations of
diazepam and
fosphenytoin were also tested for effectiveness. No dose of
fosphenytoin (18-56 mg/kg), given in conjunction with a fixed dose of
diazepam (4.8 mg/kg, i.m.) 5 min after seizure onset, enhanced the
anticonvulsant effect of
diazepam. When
fosphenytoin (18 or 32 mg/kg, i.p.) was given as a pretreatment and
diazepam was given 5 min after seizure onset, the 32 mg/kg dose of
fosphenytoin significantly reduced the time for seizure control. These studies show that
fosphenytoin, either alone or in combination with
diazepam, has little or no therapeutic
anticonvulsant effectiveness for
nerve agent-induced
status epilepticus.