Ketamine,
etomidate and
propofol modified behavioral and electrographic correlates of kindled
seizures in rats. In detail,
ketamine (5 mg/kg) and
propofol (15 mg/kg) significantly increased afterdischarge threshold, reduced seizure severity and shortened seizure and afterdischarge durations.
Etomidate (7.5 mg/kg) was effective in terms of seizure and afterdischarge durations. Moreover, the combinations of
ketamine (2.5 mg/kg) with
carbamazepine (15 mg/kg) or
valproate (50 mg/kg; all drugs at their subeffective doses), reduced the severity and duration of kindled
seizures. The antiseizure potency of the
ketamine/
carbamazepine combination was comparable to that of
carbamazepine alone administered at 20 mg/kg, while the effect of
ketamine/
valproate was comparable to the efficacy of
valproate alone at 100 mg/kg. However, the combinations of
ketamine with
phenobarbital or
diphenylhydantoin did not exert any protective action.
Propofol and
etomidate entirely failed to interact with conventional
antiepileptics. The combinations of
ketamine with
carbamazepine or
valproate did not induce any significant motor impairment in the chimney test or
memory deficit in the passive avoidance task. A pharmacokinetic interaction, at least in plasma, can be excluded, because
ketamine (2.5 mg/kg) did not affect the free plasma concentrations of
carbamazepine or
valproate. Results of the present study may suggest that there may be no risk of negative interactions between
injectable anesthetics and
antiepileptics in cases of
partial epilepsy.