The effects of two non-competitive NMDA antagonists - MK-801 and ketamine - were studied in a model of generalized seizures elicited by s.c. injection of strychnine (2 or 3 mg/kg) in adult rats. The animals were observed in isolation for 30 min after strychnine administration. Pretreatment with MK-801 (0.5 or 2 mg/kg i.p.) suppressed the tonic, but not the clonic phase of generalized seizures following both doses of strychnine. A similar action of ketamine (20 or 40 mg/kg i.p.) was indicated but it did not attain statistical significance. Strychnine-induced lethality was not changed significantly. A comparison with antiepileptic drugs demonstrated that only phénobarbital (10-80 mg/kg i.p.) was clearly effective against strychnine-induced seizures; carbamazepine (25 or 50 mg/kg i.p.) and partly phenytoin (30 or 60 mg/kg i.p.) were able to suppress the incidence of the tonic phase. Primidone (40 or 80 mg/kg i.p.) as well as the benzodiazepines bretazenil (0.1 or 1 mg/kg i.p.) and midazolam (two lower doses of 0.5 and 1 mg/kg i.p.) were without significant effect. The 2 mg/kg dose of midazolam was partly effective. Only phénobarbital, carbamazepine and the highest dose of midazolam prevented strychnine-induced lethality.
Action of antiepileptic drugs in immature brain may differ from that in adult brain. The aim of our study was to study an anticonvulsant action of lamotrigine and phenytoin, i.e. two drugs active against partial seizures in adult experimental animals as well as human patients, in a model of simple partial seizures in immature rats. Epileptic foci were induced by local application of bicuculline methiodide on sensorimotor cortical area of 12-dayold rat pups. The animals were pretreated with lamotrigine (LTG, 10 or 20 mg/kg i.p.) or phenytoin (PHT, 15, 30 or 60 mg/kg i.p.). Control rats for LTG received saline, controls for PHT solvent composed of propyleneglycol, ethanol and water. Influence of either drug on interictal activity was negligible. High doses of both LTG and PHT suppressed the transition into ictal phases and shortened the duration of persisting seizures. The tricomponent solvent exhibited moderate activity against ictal activity if compared with saline controls. The two drugs exhibited similar action in our model, i.e. the suppression of secondary generalization from epileptic focus. This action is comparable to that described for human patients and adult experimental animals. In favor of lamotrigine speaks the absence of serious side effects., K. Bernášková, P. Mareš., and Obsahuje bibliografii a bibliografické odkazy