KAINIC ACID AND 4-AMINOPYRIDINE SEIZURE MODELS IN MICE - EVALUATION OF EFFICACY OF ANTIEPILEPTIC AGENTS AND CALCIUM-ANTAGONISTS

Seizures may be induced in mice in response to stimulation of subtypes of glutamate receptors by kainic acid or inhibition of certain voltag e-dependent potassium channels by 4-aminopyridine (4-AP). The anti-sei zure efficacy of intraperitoneally administered anticonvulsants and Ca ++ antagonists to CF-1 mice was tested using these models. The order o f potency for prevention of kainate convulsions and the subsequent let hality was: dihydropyridine Ca++ antagonists (nicardipine, nisoldipine > nitrendipine > nifedipine > nimodipine) followed by verapamil > pre nylamine > diltiazem > flunarizine > remacemide HCl > ethosuximide > v alproate. In the 4-AP model the order of potency to prevent hind limb tonic extension was: MK801(+/-) > lamotrigine > phenytoin, phenobarbit al > carbamazepine > FPL 12495AA (the desglycine metabolite of remacem ide HCl), remacemide HCl > flunarizine > prenylamine > > > valproate. Therefore, compounds that limit activation of kainate receptors and vo ltage-operated linked calcium channels are active in the kainate model . Agents effective against maximal electroshock appear to be effective in the 4-AP model.