Anticonvulsant action of GABA agonists and prodrugs on minor and major seizures in epileptic gerbils. Comparison with mouse models of seizure states.

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.