This study evaluated the potency and rapidity of some
anticholinergics (
atropine,
biperiden, and
trihexyphenidyl) and
benzodiazepines (
diazepam and
midazolam) as an
anticonvulsant treatment against
seizures induced by six
nerve agents (
tabun,
sarin,
soman,
cyclosarin, VR, and
VX) and summarized the relationship between
anticonvulsant activity and
nerve agent-induced lethality and neuropathology. Guinea pigs, previously implanted with cortical
electrodes for EEG recording, were pretreated with
pyridostigmine bromide (0.026 mg/kg im) 30 min prior to challenge with 2x LD50 dose (sc) of a given
nerve agent; in a separate experiment, animals were challenged with 5x LD50 sc of
soman. One minute after agent challenge the animals were treated im with 2 mg/kg
atropine SO(4) admixed with 25 mg/kg
2-PAM Cl. Five minutes after the start of EEG
seizures, animals were treated im with different doses of
anticholinergics or
benzodiazepines and observed for seizure termination. The time to seizure onset, the time to seizure termination, and 24-h lethality were recorded. The
anticonvulsant ED50 of each
drug for termination of
seizures induced by each agent was calculated and compared. Brain tissue from animals that survived 24 h was examined for pathology. All drugs were capable of terminating seizure activity, with
midazolam and
trihexyphenidyl being significantly more potent than the other drugs, and
midazolam being more rapid in controlling seizure than
atropine,
trihexyphenidyl, or
diazepam against each agent.
Seizures induced by
sarin or
VX required lower doses of all the test
anticonvulsants. The dose of a given
drug that was an effective
anticonvulsant against a 2x LD50 challenge of
soman was equally effective against
seizures induced by a 5x LD50 challenge. All
nerve agents were capable of producing neuropathology. Seizure control was strongly associated with protection against acute lethality and brain pathology.