ANTICONVULSIVE ACTIVITY OF A NEW GABA MIMETIC DRUG

This study examines the pharmacological profile of a new GABA mimetic drug, 4-[(2H)-1,3-benzoxazine-2,4(3H)-dione]-butyric acid (BXDBA), usi ng both a behavioral and an anticonvulsive study. The behavior element s considered were locomotor activity, motor coordination, catalepsy, b ehavior and antinociception. The anticonvulsive study was performed us ing the convulsive agent bicuculline. BXDBA [10, 20 and 40 mg/kg, intr aperitoneally (i.p.)] did not significantly modify animal behavior or the nociceptive threshold of the animals. The anticonvulsive study ind icated that BXDBA (10, 20 and 40 mg/kg, i.p.), injected 60 min before bicuculline (10 mu g/intracerebroventricular (i.c.v.)/mouse) induced a dose-dependent and significant reduction of the convulsive activity o f bicuculline whereas it was ineffective if injected immediately befor e the convulsive agent. Our data indicate that this new GABA mimetic d rug possesses good anticonvulsive activity and its ability to block bi cuculline-induced convulsions suggests that it could be a GABA(A) mime tic drug. Furthermore, since BXDBA is able to act after systemic admin istration, our data suggest that this new GABA mimetic drug crosses th e blood-brain barrier. (C) 1997 Elsevier Science B.V.