Xu J H, Cao H, Zheng J H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Zhejiang Medical University, Hangzhou.
Yao Xue Xue Bao. 1993;28(11):801-7.
Intracerebral-ventricular (icv) injection of 4-aminopyridine (4-AP) 8 micrograms to rabbits generated convulsions and epileptic discharges in electrocorticogram (ECoG). With 40 rabbits, the occurrence of convulsion at this dose level was 100%. The results from five rabbits showed that seizures may break out repeatedly at intervals of 1-5 min and such state may last about 1.5 h. Antiepileptic drugs, such as phenytoin sodium, phenobarbital sodium and diazepam, were found to effectively control the seizures provoked by icv 4-AP. Sodium valproate was less effective than the foregoing drugs. The icv 4-AP-induced convulsion appeared to have some merits as compared with the old epilepsy models, such as those induced by electric stimulation, cardiazol, or icv ferrous sulfate. We feel that it may be recommended as a model for the preliminary screening of antiepileptic drugs. The seizures provoked by icv 4-AP were shown to be antagonized by scopolamine, haloperidol, phentolamine, or propranolol, but potentiated by l-dopa. It is now recognized that 4-AP can enhance the release of ACh, DA, and NE in the central nervous system. The present results suggest that the convulsion elicited by 4-AP seems to be related to the disturbance of synaptic transmission in the brain.
向家兔脑室内注射8微克4-氨基吡啶（4-AP）可引发惊厥，并在脑电图（ECoG）上出现癫痫样放电。在40只家兔中，此剂量水平下惊厥的发生率为100%。来自5只家兔的结果显示，惊厥可能每隔1 - 5分钟反复发作，且这种状态可能持续约1.5小时。发现抗癫痫药物，如苯妥英钠、苯巴比妥钠和地西泮，可有效控制脑室内注射4-AP引发的惊厥。丙戊酸钠的效果不如上述药物。与旧的癫痫模型，如电刺激、戊四氮或脑室内注射硫酸亚铁诱导的模型相比，脑室内注射4-AP诱导的惊厥似乎有一些优点。我们认为它可推荐作为抗癫痫药物初步筛选的模型。已表明东莨菪碱、氟哌啶醇、酚妥拉明或普萘洛尔可拮抗脑室内注射4-AP引发的惊厥，但左旋多巴可使其增强。现已认识到4-AP可增强中枢神经系统中乙酰胆碱、多巴胺和去甲肾上腺素的释放。目前的结果表明，4-AP引发的惊厥似乎与脑内突触传递的紊乱有关。
