EFFECTS OF NNC-711, A GABA UPTAKE INHIBITOR, ON PENTYLENETETRAZOL-INDUCED SEIZURES IN DEVELOPING AND ADULT RATS

The anticonvulsant action of NNC 711 [(1-(2((diphenylmethylene) amino) oxy) ethyl)-1,2,4,6-tetrahydro-3-pyridinecarboxylic acid hydrochlorid e], an inhibitor of the GABA transporter GAT-1, was studied in a model of pentylenetetrazol-induced motor seizures in rats 7, 12, 18, 25, an d 90 days old. NNC 711 at doses of 0.25-20 mg/kg i.p. exhibited two ef fects in rat pups: a suppression of minimal clonic seizures in age gro ups in which this type of seizure could be reliably elicited (i.e. in rats aged 18 and 25 days); and a specific suppression or restriction o f the tonic phase of generalized tonic-clonic seizures (GTCS) expresse d in 18- and especially 12-day-old rats. Effects of NNC 711 on GTCS in 7- and 25-day-old rats were irregular. Adult (i.e. 90-day-old) animal s exhibited abolition of generalized tonic-clonic seizures. minimal cl onic seizures were suppressed only after substantially higher doses. T he abolition of minimal seizures by doses too low to influence general ized tonic-clonic seizures as observed in rat pups is unique among ant iepileptic drugs. In addition, an EEG study in rat pups demonstrated d issociation of EEG signs and motor seizures in some animals.