The aims of the present study were to investigate the
anticonvulsant activity and behavioral toxicity of
FrPbAII using freely moving Wistar rats. Moreover, the effectiveness of this compound against chemical
convulsants was compared to that of the inhibitor of the GABAergic uptake,
nipecotic acid. Our results show that
FrPbAII was effective against
seizures induced by the i.c.v. injection of
pilocarpine (ED(50) = 0.05 microg/animal),
picrotoxin (ED(50) = 0.02 microg/animal),
kainic acid (ED(50) = 0.2 microg/animal) and the systemic administration of PTZ (ED(50) = 0.03 microg/animal). The
anticonvulsant effect of
FrPbAII differed from that of
nipecotic acid in potency, as the doses needed to block the
seizures were more than 10 folds lower. Toxicity assays revealed that in the rotarod, the toxic dose of the
FrPbAII is 1.33 microg/animal, and the therapeutic indexes were calculated for each
convulsant. Furthermore, the spontaneous locomotor activity of treated animals was not altered when compared to control animals but differed from the animals treated with
nipecotic acid. Still,
FrPbAII did not induce changes in any of the behavioral parameters analyzed. Finally, when tested for
cognitive impairments in the Morris water maze, the i.c.v. injection of
FrPbAII did not alter escape latencies of treated animals. These findings indicate that the novel
GABA uptake inhibitor is a potent
anticonvulsant with mild side-effects when administered to Wistar rats.