title: Anticonvulsant action of GABA agonists and prodrugs on minor and major seizures in epileptic gerbils. Comparison with mouse models of seizure states.
abstract: The anticonvulsant efficacy of the GABAmimetic drugs cetyl GABA, progabide and THIP (4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridine-3-ol) was studied against minor (myoclonic) and major (generalized tonic-clonic) seizures in gerbils as well as against maximal electroshock and s.c. pentylenetetrazol-induced seizures in mice. Seizures in gerbils were evoked by a blast of compressed air. THIP and progabide were about equally active to protect gerbils against minor and major seizures. ED 50s for THIP were 0.98 and 1.3 mg/kg and for progabide 58 and 50 mg/kg i.p., respectively. Cetyl GABA failed to show a linear dose-response against minor seizures but was quite potent against major ones (ED 50 4.4 mg/kg). All three GABAmimetics were inactive in the mouse models of seizure states except a weak effect of progabide against maximal electroshock seizures. The data show that seizure-prone gerbils with different seizure types differ strikingly in sensitivity to GABAmimetic drugs from traditional mouse models for anticonvulsant drug evaluation.
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004597:Electroshock; D005260:Female; D005849:Gerbillinae; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000494:pharmacology; D051379:Mice; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013045:Species Specificity; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; C017985:progabide; D005680:gamma-Aminobutyric Acid; C015542:gaboxadol; D010433:Pentylenetetrazole