Kainic acid and 4-aminopyridine seizure models in mice: evaluation of efficacy of anti-epileptic 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 voltage-dependent potassium channels by 4-aminopyridine (4-AP). The anti-seizure efficacy of intraperitoneally administered anticonvulsants and Ca++ antagonists to CF-1 mice was tested using these models. The order of potency for prevention of kainate convulsions and the subsequent lethality was: dihydropyridine Ca++ antagonists (nicardipine, nisoldipine > nitrendipine > nifedipine > nimodipine) followed by verapamil > prenylamine > diltiazem > flunarizine > remacemide HCl > ethosuximide > valproate. In the 4-AP model the order of potency to prevent hind limb tonic extension was: MK801(+/-) > lamotrigine > phenytoin, phenobarbital > carbamazepine > FPL 12495AA (the desglycine metabolite of remacemide HCl), remacemide HCl > flunarizine > prenylamine >>> valproate. Therefore, compounds that limit activation of kainate receptors and voltage-operated linked calcium channels are active in the kainate model. Agents effective against maximal electroshock appear to be effective in the 4-AP model.
Cramer
C L
CL
Biology Department, Fisons Pharmaceuticals, Rochester, NY 14603.
Stagnitto
M L
ML
Knowles
M A
MA
Palmer
G C
GC
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D012640:Seizures / Q000139:chemically induced*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D016291:Dizocilpine Maleate; D015761:4-Aminopyridine; D007608:Kainic Acid