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一种用于测试抗惊厥药物的灵长类动物模型。

A primate model for testing anticonvulsant drugs.

作者信息

Meldrum B S, Horton R W, Toseland P A

出版信息

Arch Neurol. 1975 May;32(5):289-94. doi: 10.1001/archneur.1975.00490470033003.

Abstract

Senegalese baboons (Papio papio), with a natural syndrome of photosensitive epilepsy, consistently show generalized myoclonic jerks if stimulated stroboscopically at hourly intervals, two to eight hours after the intravenous administration of allylglycine, 200 mg/kg. This provides a model for testing the acute antiepileptic effects of established or new drugs. The relationship between concentration of drug, antiepileptic action, and acute neurological toxic effects can be studied. Pnehobarbital (15 mg/kg) and diazepam (0;5 to 1.5 mg/kg) were highly effective in the absence of signs of toxic reaction (plasma levels: phenobarbital sodium, 0.7 to 1.7 mg/100 ml; diazepam, greater than 0.5 mug/ml). After administration of carbamazepine (30 to 40 mg/kg) and diphenylhydantoin sodium (40 to 50 mg/kg), antiepileptic action was seen, but was accompanied by severe toxic signs (nystagmus and ataxia). Sulthiame (20 to 125 mg/kg) and ethosuximide (50 to 100 mg/kg) had little antiepileptic activity and no acute toxic effects. This primate model may aid the identification of new drugs that are active against grand mal seizures and status epilepticus.

摘要

患有光敏性癫痫自然综合征的塞内加尔狒狒(巴氏狒狒),在静脉注射200毫克/千克烯丙基甘氨酸后两到八小时,如果每隔一小时用频闪灯刺激,会持续出现全身性肌阵挛性抽搐。这为测试已上市或新药的急性抗癫痫作用提供了一个模型。可以研究药物浓度、抗癫痫作用和急性神经毒性作用之间的关系。苯巴比妥(15毫克/千克)和地西泮(0.5至1.5毫克/千克)在没有毒性反应迹象的情况下非常有效(血浆水平:苯巴比妥钠,0.7至1.7毫克/100毫升;地西泮,大于0.5微克/毫升)。给予卡马西平(30至40毫克/千克)和苯妥英钠(40至50毫克/千克)后,可见抗癫痫作用,但伴有严重的毒性体征(眼球震颤和共济失调)。舒噻美(20至125毫克/千克)和乙琥胺(50至100毫克/千克)几乎没有抗癫痫活性,也没有急性毒性作用。这种灵长类动物模型可能有助于鉴定对大发作和癫痫持续状态有效的新药。

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