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), using both a behavioral and an anticonvulsive study. The behavior elements considered were locomotor activity, motor coordination, catalepsy, behavior and antinociception. The anticonvulsive study was performed using the convulsive agent bicuculline. BXDBA [10, 20 and 40 mg/kg, intraperitoneally (i.p.)] did not significantly modify animal behavior or the nociceptive threshold of the animals. The anticonvulsive study indicated that BXDBA (10, 20 and 40 mg/kg, i.p.), injected 60 min before bicuculline (10 micrograms/intracerebroventricular (i.c.v.)/mouse) induced a dose-dependent and significant reduction of the convulsive activity of bicuculline whereas it was ineffective if injected immediately before the convulsive agent. Our data indicate that this new GABA mimetic drug possesses good anticonvulsive activity and its ability to block bicuculline-induced convulsions suggests that it could be a GABAA mimetic drug. Furthermore, since BXDBA is able to act after systemic administration, our data suggest that this new GABA mimetic drug crosses the blood-brain barrier.
Capasso
A
A
School of Pharmacy, University of Salerno, Italy.
Biondi
A
A
Palagiano
F
F
Bonina
F P
FP
Montenegro
L
L
de Caprariis
P
P
Pistorio
E
E
Sorrentino
L
L
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced; D003292:Convulsants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D010078:Oxazines / Q000008:administration & dosage / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
C106730:4-((2H)-1,3-benzoxazine-2,4(3H)-dione)butyric acid; D000700:Analgesics; D000927:Anticonvulsants; D003292:Convulsants; D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D010078:Oxazines; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline