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一种用于药物研究的新实验模型:苯巴比妥和苯妥英对外侧膝状体点燃猫光敏性的影响

A new experimental model for drug studies: effects of phenobarbital and phenytoin on photosensitivity in the lateral geniculate-kindled cat.

作者信息

Wada Y, Okuda H, Yoshida K, Hasegawa H, Jibiki I, Kido H, Yamaguchi N

机构信息

Department of Neuropsychiatry, Kanazawa University School of Medicine, Japan.

出版信息

Epilepsia. 1987 Nov-Dec;28(6):667-72. doi: 10.1111/j.1528-1157.1987.tb03698.x.

Abstract

Photosensitivity was acquired as a result of kindling in the lateral geniculate body (GL), and the GL-kindled cat pretreated with DL-allylglycine showed a stable level of photosensitivity. To test the usefulness as a model for the evaluation of anticonvulsant drugs, the effects of phenobarbital (PB) and phenytoin (PHT) on photosensitivity were studied in the GL-kindled cat under DL-allylglycine. PB (5 and 10 mg/kg intravenously, i.v.) completely suppressed photically induced seizures in most subjects at plasma concentrations of 7-16 micrograms/ml, and this anticonvulsant action persisted for at least 4 h after the injection. PHT (15 mg/kg, i.v.) at plasma concentrations of 9-15 micrograms/ml produced toxic signs, e.g., pupil dilatation, hypersalivation, and tachypnea. At this dose, PHT was inactive against photically induced myoclonus but prevented the elicitation of a generalized tonic-clonic convulsion. From these results showing that the effects of anticonvulsant drugs on photically induced seizures can be assessed in relation to plasma concentration and acute neurologic toxicity, we suggest that the GL-kindled cat is a potentially useful animal model of epilepsy for testing the efficacy of anticonvulsant drugs.

摘要

光敏感性是通过外侧膝状体(GL)点燃诱导产生的,经DL-烯丙基甘氨酸预处理的GL点燃猫表现出稳定的光敏感性水平。为了测试其作为评估抗惊厥药物模型的实用性,在DL-烯丙基甘氨酸作用下,研究了苯巴比妥(PB)和苯妥英(PHT)对GL点燃猫光敏感性的影响。PB(静脉注射5和10mg/kg)在血浆浓度为7-16μg/ml时,可在大多数实验对象中完全抑制光诱导的癫痫发作,且这种抗惊厥作用在注射后至少持续4小时。PHT(静脉注射15mg/kg)在血浆浓度为9-15μg/ml时产生毒性体征,如瞳孔散大、流涎过多和呼吸急促。在此剂量下,PHT对光诱导的肌阵挛无作用,但可防止全身性强直-阵挛性惊厥的诱发。从这些结果表明抗惊厥药物对光诱导癫痫发作的影响可根据血浆浓度和急性神经毒性进行评估,我们认为GL点燃猫是一种潜在有用的癫痫动物模型,可用于测试抗惊厥药物的疗效。

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