Two different anticonvulsant actions of tiagabine in developing rats

Purpose: Our gc,al was to study the anticonvulsant action of tiagabine (TGB ) at different levels of brain maturation in rats. Methods: Wistar rats in five age groups (7, 12, 18, 25, and 90 days old) we re injected intraperitoneally with TGB at doses of 0.5-32 mg/kg. Thirty min utes later, motor seizures were induced by the subcutaneous adminstration o f pentylenetetrazol (PTZ) in a dose of 100 mg/kg for all of the groups exce pt the 18-day-old rat pups, which received a 90-mg/kg dose. The incidence a nd latency of two types of motor seizures, minimal clonic and generalized t onic-clonic seizures (GTCSs), were evaluated, and the seizure severity was scored. The time profile of TGB action at the 8-mg/kg dose was studied in t he 12- and 25-day-old rats. Results: Minimal clonic seizures were reliably induced in rats 18 days old or older, and the seizures were suppressed by TGB in all of these age group s. Although TGB was very effective against this type of seizure in the 18-d ay-old rats, the efficacy of the drug decreased with the age of the animal. GTCSs were suppressed by TGB in the adult and 25-day-old rats, and a U-sha ped dose-response curve was outlined in these two groups. The 18- and 12-da y-old rat pups exhibited a selective suppression of the tonic phase of GTCS s. A mixture of these two effects was observed in the youngest group. TGB d emonstrated a markedly longer action in the 12-day-old rats than in the 25- day-old rats. Conclusions: TGB exhibits anticonvulsant action against both minimal seizur es and GTCSs. Ontogenetic develop ment of these two actions is markedly dif ferent.