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 significantly 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.