Results from studies based on microinfusions into seizure controlling brain sites (area tempestas, medial septum, perirhinal cortex, posterior piriform cortex) have shown that
procyclidine,
muscimol,
caramiphen, and
NBQX, but not
ketamine, exert
anticonvulsant effects against
soman-induced
seizures. The purpose of the present study was to examine whether
levetiracetam (
Keppra(®)) may enhance the
anticonvulsant potency of the above drugs to become optimally effective when used systemically.
Levetiracetam has a unique profile in preclinical models of
epilepsy and has been shown to increase the potency of other
antiepileptic drugs. The rats were pretreated with
pyridostigmine (0.1mg/kg) to enhance survival and received
anticonvulsants 20 min after onset of
seizures evoked by
soman (1.15 × LD(50)). The results showed that no single
drug was able to terminate seizure activity. However, when
levetiracetam (LEV; 50mg/kg) was combined with either
procyclidine (PCD; 10mg/kg) or
caramiphen (
CMP; 10mg/kg) complete cessation of
seizures was achieved, but the nicotinic antagonist
mecamylamine was needed to induce full motor rest in some rats. In a subsequent experiment, rats were pretreated with
HI-6 (125 mg/kg) to enhance survival and treatment started 40 min following seizure onset of a
soman dose of 1.6 × LD(50). LEV (50mg/kg) combined with either PCD (20mg/kg) or
CMP (20mg/kg) terminated seizure activity, but the survival rate was considerably higher for LEV+PCD than LEV+CMP. Both
therapies could also save the lives of rats that were about to die 5-10 min after seizure onset. Thus, the combination of LEV and PCD or
CMP may make up a model of a future autoinjector being effective regardless of the time of application.