Anticonvulsant action of topiramate against motor seizures in developing rats

Purpose: To study the anticonvulsant action of topiramate (TPM) in developi ng rats. Method: Motor seizures were elicited by administering pen tylenetetrazol (1 00 mg/kg subcutaneously) in five age groups of Wistar rats (7, 12, 18, 25, and 90 days old). TPM was administered intraperitoneally in doses from 10 t o 640 mg/kg 2 hours before pentylenetetrazol. The time course of TPM action was studied in 12- and 25-day-old rats up to 24 hours after the 160-mg/kg dose, and the incidence and pattern of seizures were evaluated. Results: TPM did not influence minimal seizures (clonus of forelimb and hea d muscles with preserved righting ability). Generalized tonic-clonic seizur es, however, were reliably changed at all developmental stages studied. The tonic phase was suppressed so that the majority of animals exhibited gener alized clonic seizures (with a loss of righting reflexes). In addition, the incidence of generalized seizures was decreased after the 20-, 40-, and 80 -mg/kg doses in the 7-day-old rat pups. The specific suppression of the ton ic phase of generalized seizures was observed up to 12 hours in the 12-day- old rat pups. The same result was obtained over 6 hours after TPM administr ation in the 25-day-old animals, and with longer intervals the incidence of generalized seizures decreased in this age group. Conclusions: TPM exhibits stable anticonvulsant action against the tonic ph ase of generalized tonic-clonic seizures throughout development. In additio n, it suppresses all phases of generalized seizures in 7-day-old rats. The anticonvulsant action of TPM lasted longer in 25-day-old than in 12-day-old rats. The two actions of TPM might be ascribed to two different mechanisms of action.