The action of progabide against motor seizures elicited by pentylenetetrazol was studied in 7-, 12-, 18-, 25-day-old and adult rats. Progabide (dissolved in dimethylsulfoxide) was injected in doses from 12.5 to 150 mg/kg i.p. 30 min before pentylenetetrazol. Minimal seizures were not affected by solvent or progabide pretreatment. The action of progabide against major, i.e. generalized tonic-clonic seizures, changed with age: adult rats exhibited a tendency to suppression of whole major seizures, whereas specific suppression of the tonic phase was observed in rat pups during the first three weeks of life. The only effect seen in 25-day-old animals was prolongation of the latency of major seizures after the highest dose of progabide.
The action of two potential anticonvulsants, CM 40907 (10-50 mg/kg i.p.) and SR 41378 (1.25-20 mg/kg i.p.) against metrazol-induced seizures was studied in rats 7, 12, 18 and 25 days old. Two types of motor seizures - minimal, clonic and major, generalized tonic-clonic - were elicited by a 100-mg/kg dose of metrazol (s.c.) and their incidence and latency were evaluated. The severity of seizures was expressed as a score on a 5-point scale. Dimethylsulfoxide, an organic solvent, exhibited anticonvulsant action only in doses far exceeding those used for dissolving the two anticonvulsants. Both drugs suppressed minimal as well as major seizures in all age groups studied in a dose-dependent manner, SR 41378 being approximately four times more potent than CM 40907. The latencies could be measured only in animals given low doses of anticonvulsants. CM 40907 did not change the latencies whereas SR 41378 prolonged them. The severity of seizures was decreased again in a dose-dependent manner. There were only minor changes in the efficacy of CM 40907 among the four age groups. On the contrary, SR 41378 exhibited an extreme efficacy in 7-day-old rat pups, where even the 1.25 mg/kg dose signifcantly decreased the incidence and severity of seizures. The efficacy in the remaining three age groups was approximately at the same level as in adult rats.
Effect of phénobarbital (PhB, 20 and/or 40 mg/kg) on epileptic ECoG phenomena induced by metrazol was studied in acute experiments in rats aged 7, 12, 18, 25 and 90 days. Fractionated administration of metrazol (20 mg/kg i.p. each 300 s) was used to quantify the effects of PhB. First signs of metrazol action (sharp elements and/or rhythmic metrazol activity) were not reliably influenced by PhB. On the contrary, the latency of the first EEG seizures as well as of the first generalized EEG seizures was prolonged and thus a dose necessary for their elicitation was increased in all age groups. These differences reached statistical significance in 12-, 18- and 25-day-old rats. A lack of effect of PhB against the rhythmic metrazol activity supports the adequacy of this activity as a model of human absences. Differences between the development of antiepileptic and hypnotic effects of PhB (described earlier) suggest two different mechanisms of action.