Anticonvulsant activity of the glial GABA uptake inhibitor, THAO, in chemical seizures.
The antiseizure activity of the glia-selective GABA uptake inhibitor, 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepin-3-ol (THAO), was evaluated in rats in models of acute chemoconvulsion. In these experiments, intracerebroventricular administration of the drug 30 min prior to testing in doses between 100-750 micrograms provided protection against maximal pentylenetetrazol seizures and increased the latency to isonicotinic acid hydrazide seizures. Pentylenetetrazol seizure thresholds, in contrast, were not significantly elevated. The ability of THAO to suppress tonic but not generalized minor seizures suggests that it may block seizure spread.
Gonsalves
S F
SF
Department of Surgery, Dartmouth-Hitchcock Medical Center, Hanover, NH 03756.
Twitchell
B
B
Harbaugh
R E
RE
Krogsgaard-Larsen
P
P
Schousboe
A
A
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D007538:Isoniazid; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D009420:Nervous System / Q000187:drug effects; D009457:Neuroglia / Q000378:metabolism*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D007555:Isoxazoles; D014179:Neurotransmitter Uptake Inhibitors; D010080:Oxazoles; D005680:gamma-Aminobutyric Acid; C026803:5,6,7,8-tetrahydro-4H-isoxazolo(4,5-c)azepin-3-ol; D007538:Isoniazid; D010433:Pentylenetetrazole