Vigabatrin versus carbamazepine and phenytoin in kainic acid-treated pubescent rats

The effects of the administration of two doses (1,000 and 1,500 mg kg(-1)) of gamma-vinyl-GABA (GVG), have been tested in pubescent rats, systemically injected with kainic acid (KA). The changes in spontaneous behaviour before KA injection, the behavioural and epileptic manifestations (Wet Dog Shakes, Limbic Seizures and Status Epilepticus) and the lethality rate caused by KA were taken into account and compared to those observed in controls and in carbamazepine (CBZ) or phenytoin (PHT) treated animals. While GVG appeared to reduce the incidence of the epileptic manifestations and the subsequent mortality, particularly when higher doses of the drug were used, CBZ exerted a proconvulsant action and PHT did not substantially modify the parameters considered. Moreover, GVG, but not CBZ and PHT, induced remarkable sedative effects which disappeared within 48 h. The different anticonvulsant profile of GVG, CBZ and PHT were correlated to their different modes of action, since GVG acts by enhancing the inhibitory GABA-mediated processes, while CBZ and PHT act by reducing the excitatory processes. (C) 1997 The Italian Pharmacological Society.