Anticonvulsant activity of the glial-selective GABA uptake inhibitor, THPO.

The intramuscular administration of 4,5,6,7-tetrahydroisoxazolo [4,5-c] pyridin-3-ol (THPO) delayed the onset of isonicotinic acid hydrazide-induced seizures in very young chicks but not in adult mice, the difference being due to the state of development of the blood-brain-barrier which controls access of the drug to the brain tissue. THPO was also effective in preventing seizures induced in epileptic chicks by intermittent photic stimulation. The anticonvulsant action after combined administration of THPO and gabaculine, an inhibitor of GABA-alpha-oxoglutarate aminotransferase activity, was no greater than the anticonvulsant action of gabaculine alone.