In order to shorten the list of candidate drugs with
anticonvulsant potential against
nerve agents, critical subreceptors in seizure controlling brain regions should be specified. Epileptiform activity does not spread randomly throughout the brain, but appears to be generated and propagated by specific anatomical routes.
Nerve agents evoke seizure activity in the forebrain that progresses to the hind brain resulting in
tonic-clonic convulsions. In some recent studies, it was shown that lesion of the area tempestas (AT), medial septum (MS), perirhinal cortex (PRC), or posterior piriform cortex (PPC) produces
anticonvulsant effects (prevention of convulsions or delayed onset of convulsions) in rats exposed to
soman, whereas damage to nucleus accumbens, nucleus basalis magnocellularis, amygdala, hippocampus, or entorhinal cortex does not cause
anticonvulsant impact. These results are in compliance with findings that
seizures can be generated in AT, MS, PRC, and PPC by means of
nerve agents, chemoconvulsants, or kindling. Results from microinfusion studies show that
anticonvulsant efficacy is obtained by
GABA(A) modulators or
cholinergic antagonists (M1-M5) in AT,
cholinergic antagonists (M1-M5) in MS, combined glutamatergic (
NMDA) and
cholinergic antagonist (M1-M4),
AMPA antagonist, or modulators of
metabotropic glutamate receptors (mGluR5,
mGluR2/3) in PRC, and
cholinergic antagonist (M1-M5) or
GABA(A) agonist in PPC. Calculation of impact factors for the most potent drugs (percentage of positive effects in the seizure controlling sites) showed that
scopolamine and
procyclidine were ranking highest (75) followed by
muscimol (50),
NBQX (33), and
caramiphen (33). Potential strategies for prophylactic and post-exposure treatments are discussed.