EFFECTS OF ANTICONVULSANT DRUGS ON 4-AMINOPYRIDINE-INDUCED SEIZURES IN MICE

被引:143
作者
YAMAGUCHI, S [1 ]
ROGAWSKI, MA [1 ]
机构
[1] NINCDS,EPILEPSY RES BRANCH,NEURONAL EXCITABIL SECT,BLDG 10,ROOM 5N-248,BETHESDA,MD 20892
基金
美国国家卫生研究院;
关键词
ANTICONVULSANT DRUGS; 4-AMINOPYRIDINE; EXPERIMENTAL SEIZURES; POTASSIUM CHANNEL BLOCKER;
D O I
10.1016/0920-1211(92)90016-M
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The K+ channel blocker 4-aminopyridine (4-AP) causes epileptiform activity in in vitro preparations and is a potent convulsant in animals and man. In mice, 4-AP produces behavioral activation, clonic limb movements and wild running, followed by tonic hindlimb extension and death (ED97, 13.3 mg/kg, s.c.). We evaluated the ability of a series of anticonvulsant drugs to protect against 4-AP-induced seizures using lethality as the endpoint. Drugs with a phenytoin-like profile of activity were protective with ED50 values (all in mg/kg, i.p.) of 34.4 for phenytoin, 18.6 for carbamazepine, 26.9 for felbamate, and 41.5 for zonisamide. Phenobarbital and valproate also protected against 4-AP-induced seizures and lethality (ED50s, 30.6 and 301, respectively). In contrast the NMDA antagonists (+/-)-CPP and (+)-MK-801 were inactive as were the GABA enhancers diazepam, vigabatrin and tiagabine; the antiabsence drug ethosuximide; and the L-type Ca2+ channel blocker nimodipine. We conclude that drugs like phenytoin which block seizure spread are effective antagonists of seizures induced by K+ channel blockade. Drugs with specific actions on other cellular targets may be weak or inactive, presumably because they are unable to attenuate the spread of intense (non-NMDA receptor mediated) excitation evoked by 4-AP.
引用
收藏
页码:9 / 16
页数:8
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