A total of eight
anticholinergic drugs (
aprophen,
atropine,
azaprophen,
benactyzine,
biperiden,
procyclidine,
scopolamine,
trihexyphenidyl) were tested in parallel with
diazepam for the ability to terminate seizure activity induced by the
nerve agent soman. Guinea pigs, implanted with
electrodes to record cortical electroencephalographic (EEG) activity, were pretreated with
pyridostigmine Br (0.026 mg/kg, i.m.) and 30 min later challenged with 2 x LD50
soman (56 microg/kg, s.c.) followed 1 min later by treatment with
atropine SO4 (2 mg/kg, i.m.) and
pralidoxime chloride (2-PAM Cl; 25 mg/kg, i.m.). All guinea pigs developed sustained seizure activity following this treatment. Dose-effect curves were determined for the ability of each
drug to terminate seizure activity when
anticonvulsant treatment was given either 5 or 40 min after seizure onset.
Body weight gain and recovery of behavioral performance of a previously trained one-way avoidance task were measured after exposure. With the exception of
atropine, all
anticholinergic drugs were effective at lower doses than
diazepam in terminating
seizures when given 5 min after seizure onset;
benactyzine,
procyclidine and
aprophen terminated
seizures most rapidly while
scopolamine,
trihexyphenidyl,
biperiden, and
diazepam were significantly slower. When given 40 min after seizure onset,
diazepam was the most potent compound tested, followed by
scopolamine,
benactyzine and
biperiden;
atropine was not effective when tested 40 min after seizure onset. For
diazepam, the time to terminate the seizure was the same whether it was given at the 5- or 40-min delay. In contrast, most
anticholinergics were significantly slower in terminating seizure activity when